{"entity": "researcher", "timestamp": "2026-07-18T02:55:09.618Z", "family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "affiliations": ["Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.", "Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd"}}, "publications": [{"entity": "publication", "iuid": "457495686eaa4727b243b252d2f4e6fe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/457495686eaa4727b243b252d2f4e6fe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/457495686eaa4727b243b252d2f4e6fe"}}, "title": "Characterization of CTNND2-related neurodevelopmental disease, phenotype-genotype spectrum and WNT dynamics in early neurogenesis.", "authors": [{"family": "Shahsavani", "given": "Mansoureh", "initials": "M"}, {"family": "Wincent", "given": "Josephine", "initials": "J", "orcid": "0000-0002-1698-9605", "researcher": {"href": "https://publications.scilifelab.se/researcher/57e9777724444021924229d3fdc8673e.json"}}, {"family": "Reiter", "given": "Ricarda", "initials": "R"}, {"family": "Soltysova", "given": "Andrea", "initials": "A"}, {"family": "Schuy", "given": "Jakob", "initials": "J"}, {"family": "Helgadottir", "given": "Hafdis T", "initials": "HT", "orcid": "0000-0003-4352-152X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce4dc1001c944a9d9dfe4c092cfda497.json"}}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications.scilifelab.se/researcher/32a701ee07674785b48b047665e18ee6.json"}}, {"family": "Ek", "given": "Marlene", "initials": "M"}, {"family": "Ficek", "given": "Andrej", "initials": "A"}, {"family": "Druschke", "given": "Lotta", "initials": "L"}, {"family": "Kusikova", "given": "Katarina", "initials": "K"}, {"family": "Hsieh", "given": "Tzung-Chien", "initials": "TC"}, {"family": "Krichhoff", "given": "Aron", "initials": "A"}, {"family": "Krawitz", "given": "Peter", "initials": "P"}, {"family": "Li", "given": "Jing-Mei", "initials": "JM"}, {"family": "Webersinke", "given": "Gerald", "initials": "G"}, {"family": "Gorokhova", "given": "Svetlana", "initials": "S"}, {"family": "Missirian", "given": "Chantal", "initials": "C"}, {"family": "Riccardi", "given": "Florence", "initials": "F"}, {"family": "Pavinato", "given": "Lisa", "initials": "L"}, {"family": "Brusco", "given": "Alfredo", "initials": "A", "orcid": "0000-0002-8318-7231", "researcher": {"href": "https://publications.scilifelab.se/researcher/80fa6038bda54597ac495d278d106511.json"}}, {"family": "Mandrile", "given": "Giorgia", "initials": "G"}, {"family": "Trajkova", "given": "Slavica", "initials": "S"}, {"family": "Pintus", "given": "Francesco", "initials": "F"}, {"family": "Gagachovska", "given": "Biljana", "initials": "B"}, {"family": "Waisfisz", "given": "Quinten", "initials": "Q"}, {"family": "van Hagen", "given": "Annet", "initials": "A"}, {"family": "Bedoukian", "given": "Emma", "initials": "E"}, {"family": "Izumi", "given": "Kosuke", "initials": "K"}, {"family": "Granger", "given": "Leslie", "initials": "L"}, {"family": "Petersen", "given": "Andrea", "initials": "A", "orcid": "0000-0003-3882-0867", "researcher": {"href": "https://publications.scilifelab.se/researcher/69701b12d455487a9dd1ab55f9904327.json"}}, {"family": "Oegema", "given": "Renske", "initials": "R", "orcid": "0000-0002-7146-617X", "researcher": {"href": "https://publications.scilifelab.se/researcher/246eec36818e410296fd2d6ea502483f.json"}}, {"family": "Huibers", "given": "Manon", "initials": "M"}, {"family": "Demurger", "given": "Florence", "initials": "F"}, {"family": "Brischoux-Boucher", "given": "Elise", "initials": "E"}, {"family": "Julia", "given": "Sophie", "initials": "S"}, {"family": "Banneau", "given": "Guillaume", "initials": "G"}, {"family": "Zavala", "given": "M Jesus", "initials": "MJ"}, {"family": "Lagos", "given": "Catalina", "initials": "C"}, {"family": "Repetto", "given": "Gabriela M", "initials": "GM"}, {"family": "Jouret", "given": "Guillaume", "initials": "G"}, {"family": "Kentros", "given": "Catherine", "initials": "C"}, {"family": "Ganapathi", "given": "Mythily", "initials": "M"}, {"family": "Chung", "given": "Wendy K", "initials": "WK"}, {"family": "May", "given": "Halie", "initials": "H"}, {"family": "Hiatt", "given": "Susan M", "initials": "SM"}, {"family": "Kelley", "given": "Whitley V", "initials": "WV"}, {"family": "F\u00f6rster", "given": "Alisa", "initials": "A"}, {"family": "Olfe", "given": "Lisa", "initials": "L"}, {"family": "Shillington", "given": "Amelle", "initials": "A"}, {"family": "Dauriat", "given": "Benjamin", "initials": "B"}, {"family": "Mercier", "given": "Sandra", "initials": "S"}, {"family": "Cogn\u00e9", "given": "Benjamin", "initials": "B", "orcid": "0000-0002-5503-6292", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f0dea78166143c38c60c12206444207.json"}}, {"family": "Engel", "given": "Camille", "initials": "C"}, {"family": "Dahlen", "given": "Eric", "initials": "E"}, {"family": "Rosenberger", "given": "Georg", "initials": "G"}, {"family": "Sauvigny", "given": "Thomas", "initials": "T"}, {"family": "Abdallah", "given": "Hamza Hadj", "initials": "HH"}, {"family": "Courtin", "given": "Thomas", "initials": "T"}, {"family": "Stray-Pedersen", "given": "Asbj\u00f8rg", "initials": "A"}, {"family": "Bernat", "given": "John A", "initials": "JA"}, {"family": "Paolillo", "given": "Vitoria K", "initials": "VK"}, {"family": "Viso", "given": "Florencia Del", "initials": "FD"}, {"family": "Alaimo", "given": "Joseph T", "initials": "JT"}, {"family": "Thiffault", "given": "Isabelle", "initials": "I"}, {"family": "Farrow", "given": "Emily G", "initials": "EG"}, {"family": "Cohen", "given": "Ana S A", "initials": "ASA"}, {"family": "Weis", "given": "Serge", "initials": "S"}, {"family": "Duba", "given": "Hans-Christoph", "initials": "HC"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Falk", "given": "Anna", "initials": "A", "orcid": "0000-0003-1634-8610", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b708dfb7f0548589bdee53d6e6b536e.json"}}, {"family": "Weis", "given": "Denisa", "initials": "D"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}], "type": "journal article", "published": "2025-12-30", "journal": {"title": "Res Sq", "issn": "2693-5015", "issn-l": null}, "abstract": "Heterozygous variants in CTNND2, encoding the brain-specific protein \u03b4-catenin, are associated with a broad spectrum of neurodevelopmental disorders, including dyslexia, attention deficit hyperactivity disorder, intellectual disability, and autism. Despite its clinical significance, the full phenotypic spectrum of CTNND2-associated disorders and the neurodevelopmental role of \u03b4-catenin, a key component of the cadherin-catenin cell adhesion complex, remain poorly defined.\n\nThrough international collaboration, we assembled the phenotypic and molecular information for 57 individuals, 42 previously unpublished, carrying heterozygous CTNND2 variants. All individuals were evaluated by local clinicians, and the variants were identified through exome or genome sequencing, clinical microarray, or karyotyping. To investigate the effects of \u03b4-catenin loss on early neurogenesis, we performed neural differentiation and transcriptomic profiling in three patient-derived neural stem cell lines and three CRISPR-Cas9-generated CTNND2 knockout lines. In one patient-derived line, we further analyzed cerebral organoid development and performed pathway modulation to assess phenotypic rescue.\n\nThe 41 CTNND2 variants included 12 previously reported loss-of-function- and one missense variant, and 28 novel variants comprising 10 missense and 18 predicted loss-of-function changes. Eight of the novel variants occurred de novo, and 12 were inherited from a parent with a neurodevelopmental phenotype. The most common clinical features were developmental delay (90%), intellectual disability (74%), and behavioral abnormalities (79%). Functional studies revealed impaired early neurogenesis in one patient-derived line, characterized by aberrant neural rosette formation. Transcriptome analysis showed dysregulated WNT signaling, and partial rescue of these defects was achieved by modulating the WNT pathway, highlighting \u03b4-catenin's role in early neural development.\n\nThis study defines the clinical symptoms of CTNND2-related neurodevelopmental disorders, outlining a recognizable yet variable phenotype that overlaps with other forms of intellectual disability and autism. Our findings provide preliminary evidence of genotype-phenotype correlations and highlight \u03b4-catenin's critical role in modulating WNT signaling during early neural development. These insights advance our understanding of CTNND2-associated disorders and support the importance of mechanistic studies to inform personalized diagnostics and therapies.", "doi": "10.21203/rs.3.rs-8224288/v1", "pmid": "41502569", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12772691"}, {"db": "pii", "key": "rs.3.rs-8224288"}], "notes": [], "created": "2026-01-13T10:29:57.427Z", "modified": "2026-01-25T08:39:21.323Z"}, {"entity": "publication", "iuid": "abaf1e9bf72441a4a14b06619ce812b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/abaf1e9bf72441a4a14b06619ce812b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/abaf1e9bf72441a4a14b06619ce812b3"}}, "title": "Genome sequencing in a cohort of 32 fetuses with genetic skeletal disorders.", "authors": [{"family": "Lindel\u00f6f", "given": "Hillevi", "initials": "H"}, {"family": "Hammarsj\u00f6", "given": "Anna", "initials": "A"}, {"family": "Voss", "given": "Ulrika", "initials": "U"}, {"family": "Gaetana Piticchio", "given": "Serena", "initials": "S"}, {"family": "Conner", "given": "Peter", "initials": "P"}, {"family": "Papadogiannakis", "given": "Nikos", "initials": "N"}, {"family": "Batkovskyte", "given": "Dominyka", "initials": "D", "orcid": "0000-0002-0492-1259", "researcher": {"href": "https://publications.scilifelab.se/researcher/017749b78ac540a6b2a36303130606f2.json"}}, {"family": "Orellana", "given": "Laura", "initials": "L", "orcid": "0000-0003-1927-555X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c614cf477d9044e28ae901600cc84e7d.json"}}, {"family": "Kvarnung", "given": "Malin", "initials": "M"}, {"family": "Malmgren", "given": "Helena", "initials": "H"}, {"family": "Lagerstedt Robinson", "given": "Kristina", "initials": "K"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Nishimura", "given": "Gen", "initials": "G"}, {"family": "Grigelioniene", "given": "Giedre", "initials": "G", "orcid": "0000-0001-9601-3137", "researcher": {"href": "https://publications.scilifelab.se/researcher/684864357acd490cb627f38fed3b82a4.json"}}], "type": "journal article", "published": "2025-11-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "33", "issue": "11", "pages": "1474-1483", "issn-l": "1018-4813"}, "abstract": "Approximately 200 genetic skeletal disorders can present prenatally, detectable through ultrasound abnormalities during pregnancy. Severe forms are typically identified during the first or second trimester, whereas milder phenotypes are recognized later, in the third trimester. Diagnosing skeletal dysplasia prenatally is challenging due to the large number of disorders and the overlapping clinical findings that can be detected by ultrasound. This study, conducted at Karolinska University Hospital between 2015 and 2022, examines the genetic and radiographic findings in 32 fetuses (14 female and 18 male, from unrelated families) with skeletal abnormalities detected on prenatal ultrasound and confirmed by radiographs at birth or after pregnancy termination. Fetal DNA samples from all 32 fetuses underwent singleton genome sequencing using an in silico skeletal dysplasia gene panel. As a second step, for six fetuses with molecularly unsolved diagnoses, trio genome sequencing analysis involving the fetus and both parents was performed. The diagnostic yield of genome sequencing was 72%, with pathogenic or likely pathogenic variants identified in 23 of the 32 fetuses. Additionally, four variants of uncertain significance, strongly suspected to be causative based on clinical and radiographic features, as well as structural protein analyses, were identified in four fetuses with autosomal recessive conditions. The diagnoses of five fetuses remain molecularly unsolved. In conclusion, by combining detailed phenotypic data with singleton genome sequencing we were able to reach a genetic diagnosis in 72% of 32 fetal genetic skeletal disorder cases investigated at the Karolinska University Hospital.", "doi": "10.1038/s41431-025-01886-x", "pmid": "40500351", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12583725"}, {"db": "pii", "key": "10.1038/s41431-025-01886-x"}], "notes": [], "created": "2025-11-18T20:45:58.654Z", "modified": "2025-11-28T18:04:38.525Z"}, {"entity": "publication", "iuid": "b5cadf33662a43ba963d6e97bfa96d3a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5cadf33662a43ba963d6e97bfa96d3a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5cadf33662a43ba963d6e97bfa96d3a"}}, "title": "Precision Omics Initiative Sweden (PROMISE) will integrate research with healthcare.", "authors": [{"family": "K\u00e4mpe", "given": "Anders", "initials": "A", "orcid": "0000-0002-1829-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/0785e17b57384962a0ff9bc7ecaa80c8.json"}}, {"family": "Gudmundsson", "given": "Sanna", "initials": "S"}, {"family": "Walsh", "given": "Colum P", "initials": "CP"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K"}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5", "orcid": "0000-0002-2915-4498", "researcher": {"href": "https://publications.scilifelab.se/researcher/76265c54961046e99bdb0439f9ae1d34.json"}}, {"family": "Clareborn", "given": "Anna", "initials": "A"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Edsj\u00f6", "given": "Anders", "initials": "A", "orcid": "0000-0001-8783-8284", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fae25d88855440194b9bb11b3d18bf8.json"}}, {"family": "Fioretos", "given": "Thoas", "initials": "T"}, {"family": "Ehrencrona", "given": "Hans", "initials": "H", "orcid": "0000-0002-5589-3622", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b89608a8ce941c3b9911630b4ff9720.json"}}, {"family": "Eriksson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5473-3312", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9c26578a5e548f783b9465e04fb0bfc.json"}}, {"family": "Fall", "given": "Tove", "initials": "T", "orcid": "0000-0003-2071-5866", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ed3f066719f43b291743a8bdaf3d2a0.json"}}, {"family": "Franks", "given": "Paul W", "initials": "PW", "orcid": "0000-0002-0520-7604", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ebbf40c0f7e49dd8c75a2b6cbf27276.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U", "orcid": "0000-0002-6316-3355", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8739f0f42c44019ab88a49db350a4f2.json"}}, {"family": "Haag", "given": "Margareta", "initials": "M"}, {"family": "Hagwall", "given": "Anna", "initials": "A"}, {"family": "Johansson Soller", "given": "Maria", "initials": "M"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Lu", "given": "Yi", "initials": "Y", "orcid": "0000-0001-9933-3654", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a73eafe0b0e4221a77b96800883413d.json"}}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Mel\u00e9n", "given": "Erik", "initials": "E", "orcid": "0000-0002-8248-0663", "researcher": {"href": "https://publications.scilifelab.se/researcher/3af5a23ba0a847778eea300f745cb143.json"}}, {"family": "Melin", "given": "Beatrice", "initials": "B"}, {"family": "Micha\u00eblsson", "given": "Karl", "initials": "K"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Saal", "given": "Lao H", "initials": "LH", "orcid": "0000-0002-0815-1896", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a1ec17a1d2e46e78f483f8e43f5e5f2.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Sikora", "given": "Per", "initials": "P"}, {"family": "Sundstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0003-2247-8454", "researcher": {"href": "https://publications.scilifelab.se/researcher/91a40d3c138d43f2b0d38f66be4b71c7.json"}}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Van Guelpen", "given": "Bethany", "initials": "B", "orcid": "0000-0002-9692-101X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ea901d796bc4f3fbc53f930c5021118.json"}}, {"family": "Wadelius", "given": "Mia", "initials": "M", "orcid": "0000-0002-6368-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec07b9869a1f4b77b734c5dc567dc630.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "\u00d6stling", "given": "P\u00e4ivi", "initials": "P"}, {"family": "Jacobsson", "given": "Bo", "initials": "B", "orcid": "0000-0001-5079-2374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd6968816ded4a50b1029ee3f4afbeed.json"}}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}, {"family": "Persson", "given": "Bengt", "initials": "B"}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications.scilifelab.se/researcher/b570128e641140fb964ae3241414f510.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T"}], "type": "letter", "published": "2025-06-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "issn-l": "1078-8956", "volume": "31", "issue": "6", "pages": "1730-1732"}, "abstract": null, "doi": "10.1038/s41591-025-03631-9", "pmid": "40186080", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Long read": "Collaborative", "Clinical Genomics Lund": "Service", "Bioinformatics (NBIS)": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41591-025-03631-9"}], "notes": [], "created": "2025-07-08T13:55:07.435Z", "modified": "2025-11-21T13:21:42.346Z"}, {"entity": "publication", "iuid": "11bfd5f14ab244ff92ef3f20ae9e9e15", "links": {"self": {"href": "https://publications.scilifelab.se/publication/11bfd5f14ab244ff92ef3f20ae9e9e15.json"}, "display": {"href": "https://publications.scilifelab.se/publication/11bfd5f14ab244ff92ef3f20ae9e9e15"}}, "title": "Identification of biallelic POLA2 variants in two families with an autosomal recessive telomere biology disorder.", "authors": [{"family": "Kvarnung", "given": "Malin", "initials": "M"}, {"family": "Pettersson", "given": "Maria", "initials": "M"}, {"family": "Chun-On", "given": "Pattra", "initials": "P"}, {"family": "Rafati", "given": "Maryam", "initials": "M", "orcid": "0000-0001-7118-3412", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c0841d69cd04a5ea7292b73726b408a.json"}}, {"family": "McReynolds", "given": "Lisa J", "initials": "LJ", "orcid": "0000-0002-1018-1453", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf05c99cb8d34fa2ab0f09739da95295.json"}}, {"family": "Norberg", "given": "Anna", "initials": "A"}, {"family": "Moura", "given": "Pedro Luis", "initials": "PL", "orcid": "0000-0002-0493-5394", "researcher": {"href": "https://publications.scilifelab.se/researcher/12216bfd20fa4056b844842908efc829.json"}}, {"family": "Pesonen", "given": "Ida", "initials": "I"}, {"family": "Chaireti", "given": "Roza", "initials": "R"}, {"family": "Gr\u00f6nros S\u00f6derholm", "given": "Boa", "initials": "B"}, {"family": "Burlin", "given": "Julia", "initials": "J"}, {"family": "Ryd\u00e9n", "given": "Jenny", "initials": "J"}, {"family": "Lindberg", "given": "Eva Hellstr\u00f6m", "initials": "EH"}, {"family": "Giri", "given": "Neelam", "initials": "N"}, {"family": "Savage", "given": "Sharon A", "initials": "SA", "orcid": "0000-0001-6006-0740", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ebbcf2fee6945d2b1173ff0e4109674.json"}}, {"family": "Agarwal", "given": "Suneet", "initials": "S"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Tesi", "given": "Bianca", "initials": "B", "orcid": "0000-0002-8253-2507", "researcher": {"href": "https://publications.scilifelab.se/researcher/96a994cd257c4833a4efe79e26b900ff.json"}}], "type": "journal article", "published": "2025-05-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "33", "issue": "5", "pages": "580-587", "issn-l": "1018-4813"}, "abstract": "POLA2 encodes the accessory subunit of DNA polymerase \u03b1 (pol\u03b1)/primase, which is crucial for telomere C-strand fill-in. Incomplete fill-in of the C-rich telomeric strand after DNA replication has been proposed as a mechanism for Coats plus syndrome, a phenotype within the broader spectrum of telomere biology disorders (TBD). Coats plus syndrome has so far been associated with pathogenic variants in POT1, CTC1, and STN1. Here we report the findings of biallelic deleterious rare variants in POLA2 gene detected by whole genome sequencing and segregation analysis in five young adults from two unrelated families. All five individuals displayed abnormally short telomeres and a clinical phenotype suggesting a TBD disorder with Coats plus features including retinal and gastrointestinal telangiectasias. Our results suggest POLA2 as a novel autosomal recessive gene for a TBD with Coats plus features.", "doi": "10.1038/s41431-024-01722-8", "pmid": "39616267", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12048608"}, {"db": "pii", "key": "10.1038/s41431-024-01722-8"}], "notes": [], "created": "2025-11-18T20:43:12.167Z", "modified": "2025-11-18T20:44:44.102Z"}, {"entity": "publication", "iuid": "1c4d18bc851d45a187a3f9d67b07d538", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1c4d18bc851d45a187a3f9d67b07d538.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1c4d18bc851d45a187a3f9d67b07d538"}}, "title": "Pediatric Soft Tissue Sarcoma in Limb-Girdle Muscular Dystrophy: Molecular Findings and Clinical Implications.", "authors": [{"family": "Maya-Gonz\u00e1lez", "given": "Carolina", "initials": "C", "orcid": "0000-0003-0385-475X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c08ce0ec0bf4403a7c187038cdf3ca5.json"}}, {"family": "D\u00edaz De St\u00e5hl", "given": "Teresita", "initials": "T", "orcid": "0000-0001-5933-6623", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f51158ce6e14f3b96bf16a214689d1d.json"}}, {"family": "Wessman", "given": "Sandra", "initials": "S", "orcid": "0000-0002-2035-2092", "researcher": {"href": "https://publications.scilifelab.se/researcher/f4680125750b4d949d691a745818a6f7.json"}}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Tesi", "given": "Bianca", "initials": "B", "orcid": "0000-0002-8253-2507", "researcher": {"href": "https://publications.scilifelab.se/researcher/96a994cd257c4833a4efe79e26b900ff.json"}}, {"family": "Lagerstedt-Robinson", "given": "Kristina", "initials": "K", "orcid": "0000-0001-9848-0468", "researcher": {"href": "https://publications.scilifelab.se/researcher/63d275105d9b4253944abaa311c986ee.json"}}, {"family": "Tettamanti", "given": "Giorgio", "initials": "G", "orcid": "0000-0002-5210-7219", "researcher": {"href": "https://publications.scilifelab.se/researcher/275ddc738872402aa820da4d0a3d60f0.json"}}, {"family": "Dukic", "given": "Milena", "initials": "M"}, {"family": "Poluha", "given": "Anna", "initials": "A", "orcid": "0000-0002-4716-9423", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7c9d843ebd549a7875bf10d4a16ee8b.json"}}, {"family": "Ljungman", "given": "Gustaf", "initials": "G", "orcid": "0000-0002-4949-2494", "researcher": {"href": "https://publications.scilifelab.se/researcher/addd279dba044334bc5347258b3de44d.json"}}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}], "type": "case reports", "published": "2024-12-29", "journal": {"title": "Am J Case Rep", "issn": "1941-5923", "volume": "25", "pages": "e945715", "issn-l": null}, "abstract": "BACKGROUND Limb-girdle muscular dystrophy recessive 1 (LGMDR1) is an autosomal recessive degenerative muscle disorder characterized by progressive muscular weakness caused by pathogenic variants in the CAPN3 gene. Desmoplastic small round cell tumors (DSRCT) are ultra-rare and aggressive soft tissue sarcomas usually in the abdominal cavity, molecularly characterized by the presence of a EWSR1::WT1 fusion transcript. Mouse models of muscular dystrophy, including LGMDR1, present an increased risk of soft tissue sarcomas. However, the DSRCT risk and general cancer risk in patients with LGMD is unknown. Here, we delineate the clinical, molecular, and genetic findings of a patient with LGMDR1 who developed a DSRCT. CASE REPORT The patient was a boy who was diagnosed at the age of 9 years with LGMDR1, caused by the biallelic pathogenic variants NP_000061.1:p.(Arg448Cys) and NP_000061.1:p.(Thr184ArgfsTer36) in CAPN3. At 17 years of age, a pathologic soft tissue mass was found in the right pelvis. Immunostaining was positive for Desmin and negative for Myogenin and MyoD1, and RNA sequencing showed a EWSR1::WT1 fusion transcript, confirming the diagnosis of DSRCT. The patient relapsed after 1 year and, following a second relapse, he was started on palliative treatment. No germline variants in childhood cancer predisposition genes were detected by whole genome sequencing. CONCLUSIONS We describe a patient with LGMDR1 who developed a DSRCT. Since associations between LGMD and pediatric cancer are hitherto unknown, further studies are warranted, as little information is currently published about the pediatric cancer risk in this patient group.", "doi": "10.12659/AJCR.945715", "pmid": "39733240", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11694770"}, {"db": "pii", "key": "945715"}], "notes": [], "created": "2025-11-18T20:45:04.884Z", "modified": "2025-11-18T20:45:05.321Z"}, {"entity": "publication", "iuid": "1d6fcb48918e4df8b0908e1586c7dde1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d6fcb48918e4df8b0908e1586c7dde1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d6fcb48918e4df8b0908e1586c7dde1"}}, "title": "Leveraging the T2T assembly to resolve rare and pathogenic inversions in reference genome gaps.", "authors": [{"family": "Bilgrav Saether", "given": "Kristine", "initials": "K"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Bengtsson", "given": "Jesse D", "initials": "JD"}, {"family": "Lun", "given": "Ming Yin", "initials": "MY"}, {"family": "Grochowski", "given": "Christopher M", "initials": "CM", "orcid": "0000-0002-3884-7720", "researcher": {"href": "https://publications.scilifelab.se/researcher/c94bd6d4a43e41f2990ae8b9426c0312.json"}}, {"family": "Mahmoud", "given": "Medhat", "initials": "M", "orcid": "0000-0002-2553-4231", "researcher": {"href": "https://publications.scilifelab.se/researcher/e05f2f3025d34f1e940334615a912e1e.json"}}, {"family": "Chao", "given": "Hsiao-Tuan", "initials": "HT", "orcid": "0000-0002-2854-5470", "researcher": {"href": "https://publications.scilifelab.se/researcher/b50501f9598a46d0805e6c1f7cabf21b.json"}}, {"family": "Rosenfeld", "given": "Jill A", "initials": "JA"}, {"family": "Liu", "given": "Pengfei", "initials": "P", "orcid": "0000-0002-4177-709X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8bda9fff7cc042eaa054b5257799c1f4.json"}}, {"family": "Ek", "given": "Marlene", "initials": "M"}, {"family": "Schuy", "given": "Jakob", "initials": "J"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Dai", "given": "Hongzheng", "initials": "H"}, {"family": "Undiagnosed Diseases Network", "given": "", "initials": ""}, {"family": "Hwang", "given": "James Paul", "initials": "JP"}, {"family": "Sedlazeck", "given": "Fritz J", "initials": "FJ"}, {"family": "Bi", "given": "Weimin", "initials": "W"}, {"family": "Marom", "given": "Ronit", "initials": "R"}, {"family": "Wincent", "given": "Josephine", "initials": "J"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}], "type": "journal article", "published": "2024-11-20", "journal": {"title": "Genome Res.", "issn": "1549-5469", "issn-l": "1088-9051", "volume": "34", "issue": "11", "pages": "1785-1797"}, "abstract": "Chromosomal inversions (INVs) are particularly challenging to detect due to their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations and can lead to disease by gene disruption or altering regulatory regions of dosage-sensitive genes in cis Short-read genome sequencing (srGS) can only resolve \u223c70% of cytogenetically visible inversions referred to clinical diagnostic laboratories, likely due to breakpoints in repetitive regions. Here, we study 12 inversions by long-read genome sequencing (lrGS) (n = 9) or srGS (n = 3) and resolve nine of them. In four cases, the inversion breakpoint region was missing from at least one of the human reference genomes (GRCh37, GRCh38, T2T-CHM13) and a reference agnostic analysis was needed. One of these cases, an INV9 mappable only in de novo assembled lrGS data using T2T-CHM13 disrupts EHMT1 consistent with a Mendelian diagnosis (Kleefstra syndrome 1; MIM#610253). Next, by pairwise comparison between T2T-CHM13, GRCh37, and GRCh38, as well as the chimpanzee and bonobo, we show that hundreds of megabases of sequence are missing from at least one human reference, highlighting that primate genomes contribute to genomic diversity. Aligning population genomic data to these regions indicated that these regions are variable between individuals. Our analysis emphasizes that T2T-CHM13 is necessary to maximize the value of lrGS for optimal inversion detection in clinical diagnostics. These results highlight the importance of leveraging diverse and comprehensive reference genomes to resolve unsolved molecular cases in rare diseases.", "doi": "10.1101/gr.279346.124", "pmid": "39486878", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Long read": "Collaborative", "National Genomics Infrastructure": "Collaborative", "Clinical Genomics Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11610578"}, {"db": "pii", "key": "gr.279346.124"}, {"db": "medline", "key": "9509184"}], "notes": [], "created": "2024-11-04T20:44:54.793Z", "modified": "2025-02-28T14:19:49.661Z"}, {"entity": "publication", "iuid": "46b3ed67f2a843ca94d9f62dbdd2fa42", "links": {"self": {"href": "https://publications.scilifelab.se/publication/46b3ed67f2a843ca94d9f62dbdd2fa42.json"}, "display": {"href": "https://publications.scilifelab.se/publication/46b3ed67f2a843ca94d9f62dbdd2fa42"}}, "title": "Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon.", "authors": [{"family": "Delgado-Vega", "given": "Angelica Maria", "initials": "AM", "orcid": "0000-0002-9865-0591", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5e5d5e55948460d964544438d221c34.json"}}, {"family": "Cederroth", "given": "Helene", "initials": "H", "orcid": "0000-0002-5522-3418", "researcher": {"href": "https://publications.scilifelab.se/researcher/bcdb1f50435a4fce8814882e22a69b37.json"}}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Ekholm", "given": "Katja", "initials": "K", "orcid": "0009-0005-8231-8876", "researcher": {"href": "https://publications.scilifelab.se/researcher/d36170b3e310492f8a3d6a70edbe8f24.json"}}, {"family": "Ek", "given": "Marlene", "initials": "M"}, {"family": "Thonberg", "given": "H\u00e5kan", "initials": "H"}, {"family": "Jemt", "given": "Anders", "initials": "A", "orcid": "0000-0002-2219-0197", "researcher": {"href": "https://publications.scilifelab.se/researcher/5cc562a42048411aa86ded8e0bd90852.json"}}, {"family": "Nilsson", "given": "Daniel", "initials": "D"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Bilgrav Saether", "given": "Kristine", "initials": "K"}, {"family": "H\u00f6ijer", "given": "Ida", "initials": "I"}, {"family": "Akgun-Dogan", "given": "Ozlem", "initials": "O"}, {"family": "Asano", "given": "Yui", "initials": "Y"}, {"family": "Barakat", "given": "Tahsin Stefan", "initials": "TS", "orcid": "0000-0003-1231-1562", "researcher": {"href": "https://publications.scilifelab.se/researcher/05636291c79b4835a863d66a221025c7.json"}}, {"family": "Batkovskyte", "given": "Dominyka", "initials": "D", "orcid": "0000-0002-0492-1259", "researcher": {"href": "https://publications.scilifelab.se/researcher/017749b78ac540a6b2a36303130606f2.json"}}, {"family": "Baynam", "given": "Gareth", "initials": "G", "orcid": "0000-0003-4920-9553", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd6905ffc70041b980e4398d68eb114c.json"}}, {"family": "Bodamer", "given": "Olaf", "initials": "O", "orcid": "0000-0002-7847-552X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0aa490ac1a9f44c0b73be02898f51212.json"}}, {"family": "Chetruengchai", "given": "Wanna", "initials": "W"}, {"family": "Corcoran", "given": "P\u00e1draic", "initials": "P"}, {"family": "Couse", "given": "Madeline", "initials": "M"}, {"family": "Danis", "given": "Daniel", "initials": "D", "orcid": "0000-0003-0900-3411", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a25afd9229a48968ecb47d2315b964f.json"}}, {"family": "Demidov", "given": "German", "initials": "G", "orcid": "0000-0001-9075-4276", "researcher": {"href": "https://publications.scilifelab.se/researcher/4157231d1af64838a00ee99b9d0e6676.json"}}, {"family": "Dohi", "given": "Eisuke", "initials": "E", "orcid": "0000-0002-5365-4900", "researcher": {"href": "https://publications.scilifelab.se/researcher/248bdd8187cb41899bb49aeb6f22727e.json"}}, {"family": "Erhardsson", "given": "Mattias", "initials": "M", "orcid": "0000-0002-5631-2033", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc48a126473e4b2aa69c704186c52466.json"}}, {"family": "Fernandez-Luna", "given": "Luis", "initials": "L"}, {"family": "Fujiwara", "given": "Toyofumi", "initials": "T"}, {"family": "Garg", "given": "Neha", "initials": "N"}, {"family": "Giugliani", "given": "Roberto", "initials": "R"}, {"family": "Gonzaga-Jauregui", "given": "Claudia", "initials": "C", "orcid": "0000-0002-4667-3679", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ddb6b4197874a1aab306b678a5e8a41.json"}}, {"family": "Grigelioniene", "given": "Giedre", "initials": "G", "orcid": "0000-0001-9601-3137", "researcher": {"href": "https://publications.scilifelab.se/researcher/684864357acd490cb627f38fed3b82a4.json"}}, {"family": "Groza", "given": "Tudor", "initials": "T"}, {"family": "Gunnarsson", "given": "Cecilia", "initials": "C", "orcid": "0000-0001-9474-6820", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed1a42fede5f4f6d87c20d6bb9f694de.json"}}, {"family": "Hammarsj\u00f6", "given": "Anna", "initials": "A"}, {"family": "Hammond", "given": "Charles Kumi", "initials": "CK", "orcid": "0000-0002-1482-0419", "researcher": {"href": "https://publications.scilifelab.se/researcher/029f4a915c9f494db1bc05a26feec63b.json"}}, {"family": "Hatirnaz Ng", "given": "\u00d6zden", "initials": "\u00d6", "orcid": "0000-0001-7728-6527", "researcher": {"href": "https://publications.scilifelab.se/researcher/8eb6850ea2b04ba2963f02b3fb226a6e.json"}}, {"family": "Hesketh", "given": "Sirisha", "initials": "S"}, {"family": "Hettiarachchi", "given": "Dineshani", "initials": "D"}, {"family": "Johansson Soller", "given": "Maria", "initials": "M"}, {"family": "Kirmani", "given": "Umn Ahmed", "initials": "UA"}, {"family": "Kjellberg", "given": "Martin", "initials": "M", "orcid": "0009-0004-4345-1503", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd5a1065c6b34d218484cfead66cee05.json"}}, {"family": "Kvarnung", "given": "Malin", "initials": "M"}, {"family": "Kvlividze", "given": "Oleg", "initials": "O"}, {"family": "Lagerstedt-Robinson", "given": "Kristina", "initials": "K", "orcid": "0000-0001-9848-0468", "researcher": {"href": "https://publications.scilifelab.se/researcher/63d275105d9b4253944abaa311c986ee.json"}}, {"family": "Lasko", "given": "Paul", "initials": "P", "orcid": "0000-0002-4037-3501", "researcher": {"href": 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"https://publications.scilifelab.se/researcher/48850e5606b9470caa6b130286055388.json"}}, {"family": "Makay", "given": "Prince", "initials": "P"}, {"family": "Maiga", "given": "Alassane Baneye", "initials": "AB"}, {"family": "Maya-Gonz\u00e1lez", "given": "Carolina", "initials": "C"}, {"family": "Meyn", "given": "M Stephen", "initials": "MS"}, {"family": "Neethiraj", "given": "Ramprasad", "initials": "R"}, {"family": "Nigro", "given": "Vincenzo", "initials": "V"}, {"family": "Nordgren", "given": "Felix", "initials": "F"}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Orrsj\u00f6", "given": "Sara", "initials": "S", "orcid": "0009-0008-9223-3923", "researcher": {"href": "https://publications.scilifelab.se/researcher/acd6e5385a7b4406b973a3adbed96245.json"}}, {"family": "Ottosson", "given": "Jesper", "initials": "J"}, {"family": "Ozbek", "given": "Ugur", "initials": "U", "orcid": "0000-0001-5319-0547", "researcher": {"href": "https://publications.scilifelab.se/researcher/a9f5f921edb64de6ac115abdd57e55d3.json"}}, {"family": "\u00d6zdemir", "given": "\u00d6zkan", "initials": "\u00d6"}, {"family": "Partin", "given": "Clyde", "initials": "C", "orcid": "0000-0003-3996-9604", "researcher": {"href": "https://publications.scilifelab.se/researcher/20955ec5ea6c4253beccddfdb1120135.json"}}, {"family": "Pearce", "given": "David A", "initials": "DA", "orcid": "0000-0002-0707-063X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a17879050f7949a7b91d266bd5be19da.json"}}, {"family": "Peck", "given": "Raquel", "initials": "R"}, {"family": "Pedersen", "given": "Annie", "initials": "A"}, {"family": "Pettersson", "given": "Maria", "initials": "M"}, {"family": "Pongpanich", "given": "Monnat", "initials": "M"}, {"family": "Posada de la Paz", "given": "Manuel", "initials": "M", "orcid": "0000-0002-8372-4180", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a12ab27c65a464a90606c83769b3a6f.json"}}, {"family": "Ramani", "given": "Arun", "initials": "A"}, {"family": "Romero", "given": "Juan Andres", "initials": "JA"}, {"family": "Romero", "given": "Vanessa I", "initials": "VI"}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications.scilifelab.se/researcher/b570128e641140fb964ae3241414f510.json"}}, {"family": "Saw", "given": "Aung Min", "initials": "AM"}, {"family": "Spencer", "given": "Matthew", "initials": "M"}, {"family": "Stattin", "given": "Eva-Lena", "initials": "EL"}, {"family": "Srichomthong", "given": "Chalurmpon", "initials": "C"}, {"family": "Tapia-Paez", "given": "Isabel", "initials": "I", "orcid": "0000-0002-0535-4233", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ed50bc3a5034bafbff8ee63e129fb10.json"}}, {"family": "Taruscio", "given": "Domenica", "initials": "D", "orcid": "0000-0001-5403-233X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1cc58bd63f7c43f7834c1c7b98cbc065.json"}}, {"family": "Taylor", "given": "Julie P", "initials": "JP"}, {"family": "Tkemaladze", "given": "Tinatin", "initials": "T", "orcid": "0000-0003-1924-6695", "researcher": {"href": "https://publications.scilifelab.se/researcher/8fd7bba98c164a3ca012971f7b654aeb.json"}}, {"family": "Tully", "given": "Ian", "initials": "I"}, {"family": "T\u00fcmer", "given": "Zeynep", "initials": "Z", "orcid": "0000-0002-4777-5802", "researcher": {"href": "https://publications.scilifelab.se/researcher/9f87998993834fdea81a28997ee1ce76.json"}}, {"family": "van Zelst-Stams", "given": "Wendy A G", "initials": "WAG"}, {"family": "Verloes", "given": "Alain", "initials": "A", "orcid": "0000-0003-4819-0264", "researcher": {"href": "https://publications.scilifelab.se/researcher/1326e4bc6d764442b2fd851888c84f67.json"}}, {"family": "V\u00e4sterviga", "given": "Emma", "initials": "E"}, {"family": "Wang", "given": "Sailan", "initials": "S"}, {"family": "Yang", "given": "Rachel", "initials": "R", "orcid": "0009-0009-4487-6390", "researcher": {"href": "https://publications.scilifelab.se/researcher/85caaf4cb8fb4bc6bac8129b0bed5564.json"}}, {"family": "Yamamoto", "given": "Shinya", "initials": "S", "orcid": "0000-0003-2172-8036", "researcher": {"href": "https://publications.scilifelab.se/researcher/90c060c592574ce58cda8bf0339281d7.json"}}, {"family": "Y\u00e9pez", "given": "Vicente A", "initials": "VA", "orcid": "0000-0001-7916-3643", "researcher": {"href": "https://publications.scilifelab.se/researcher/661e0ca688574056bc9952c2ccdd19a4.json"}}, {"family": "Zhang", "given": "Qing", "initials": "Q"}, {"family": "Shotelersuk", "given": "Vorasuk", "initials": "V", "orcid": "0000-0002-1856-0589", "researcher": {"href": "https://publications.scilifelab.se/researcher/645f2ef9414e4301af16d3fd7841b4a2.json"}}, {"family": "Wiafe", "given": "Samuel Agyei", "initials": "SA"}, {"family": "Alanay", "given": "Yasemin", "initials": "Y"}, {"family": "Botto", "given": "Lorenzo D", "initials": "LD"}, {"family": "Kirmani", "given": "Salman", "initials": "S"}, {"family": "Lumaka", "given": "Aim\u00e9", "initials": "A", "orcid": "0000-0002-5468-8678", "researcher": {"href": "https://publications.scilifelab.se/researcher/604f009096d94902a984f0dcef8ea9a4.json"}}, {"family": "Palmer", "given": "Elizabeth Emma", "initials": "EE", "orcid": "0000-0003-1844-215X", "researcher": {"href": "https://publications.scilifelab.se/researcher/14a2059bb4314217bdf97310285da941.json"}}, {"family": "Puri", "given": "Ratna Dua", "initials": "RD", "orcid": "0000-0003-2694-6147", "researcher": {"href": "https://publications.scilifelab.se/researcher/be27a5b2e8924201be34b890b479878d.json"}}, {"family": "Wirta", "given": "Valtteri", "initials": "V"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Buske", "given": "Orion J", "initials": "OJ", "orcid": "0000-0002-9064-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bff68f288e34d81a1412ce98556d8f2.json"}}, {"family": "Cederroth", "given": "Mikk", "initials": "M"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}], "type": "journal article", "published": "2024-11-00", "journal": {"title": "Nat. Genet.", "issn": "1546-1718", "volume": "56", "issue": "11", "pages": "2287-2294", "issn-l": "1061-4036"}, "abstract": "The first-ever Undiagnosed Hackathon was a groundbreaking event held by the Wilhelm Foundation, the Karolinska Undiagnosed Disease Program, and PhenoTips in collaboration with UDNI to solve medical mysteries and advance diagnostics for undiagnosed rare diseases. Nearly 100 healthcare professionals and researchers from 28 countries participated, working intensively for 48 hours to diagnose 10 families with undiagnosed rare diseases. This innovative approach to precision diagnostics highlighted the power of international, multidisciplinary collaboration and patient partnership, yielding promising results for patients seeking answers and benefiting the entire rare diseases community.", "doi": "10.1038/s41588-024-01941-1", "pmid": "39433890", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "National Genomics Infrastructure": "Service", "Clinical Genomics Gothenburg": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "NGI Long read": "Service", "Clinical Genomics Stockholm": "Service", "Clinical Genomics Uppsala": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS2083970"}, {"db": "pmc", "key": "PMC12198426"}, {"db": "pii", "key": "10.1038/s41588-024-01941-1"}], "notes": [], "created": "2024-10-22T07:24:36.866Z", "modified": "2025-11-20T20:34:52.025Z"}, {"entity": "publication", "iuid": "632d45cd5d4c4a929a9d60d3fed5b0c8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/632d45cd5d4c4a929a9d60d3fed5b0c8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/632d45cd5d4c4a929a9d60d3fed5b0c8"}}, "title": "Cancer Risk in Patients With Muscular Dystrophy and Myotonic Dystrophy: A Register-Based Cohort Study.", "authors": [{"family": "Maya-Gonz\u00e1lez", "given": "Carolina", "initials": "C", "orcid": "0000-0003-0385-475X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c08ce0ec0bf4403a7c187038cdf3ca5.json"}}, {"family": "Tettamanti", "given": "Giorgio", "initials": "G", "orcid": "0000-0002-5210-7219", "researcher": {"href": "https://publications.scilifelab.se/researcher/275ddc738872402aa820da4d0a3d60f0.json"}}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Skarin Nordenvall", "given": "Anna", "initials": "A"}, {"family": "Sejersen", "given": "Thomas", "initials": "T", "orcid": "0000-0001-5961-7097", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab13ad6b63424037addb7dd1afbda3b2.json"}}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}], "type": "journal article", "published": "2024-10-22", "journal": {"title": "Neurology", "issn": "1526-632X", "volume": "103", "issue": "8", "pages": "e209883", "issn-l": "0028-3878"}, "abstract": "Muscular dystrophies and myotonic disorders are genetic disorders characterized by progressive skeletal muscle degeneration and weakness. Epidemiologic studies have found an increased cancer risk in myotonic dystrophy, although the cancer risk spectrum is poorly characterized. In patients with muscular dystrophy, the cancer risk is uncertain. We aimed to determine the overall cancer risk and cancer risk spectrum in patients with muscular dystrophy and myotonic dystrophy using data from the Swedish National registers.\n\nWe performed a matched cohort study in all patients with muscular dystrophy or myotonic dystrophy born in Sweden 1950-2017 and 50 matched comparisons by sex, year of birth, and birth county per individual. The association with cancer overall and specific malignancies was estimated using stratified Cox proportional hazard models.\n\nWe identified 2,355 and 1,968 individuals with muscular dystrophy and myotonic dystrophy, respectively. No increased overall cancer risk was found in muscular dystrophy. However, we observed an increased risk of astrocytomas and other gliomas during childhood (hazard ratio [HR] 8.70, 95% CI 3.57-21.20) and nonthyroid endocrine cancer (HR 2.35, 95% CI 1.03-5.34) and pancreatic cancer (HR 4.33, 95% CI 1.55-12.11) in adulthood. In myotonic dystrophy, we found an increased risk of pediatric brain tumors (HR 3.23, 95% CI 1.16-9.01) and an increased overall cancer risk in adults (HR 2.26, CI 1.92.2.66), specifically brain tumors (HR 10.44, 95% CI 7.30-14.95), thyroid (HR 3.92, 95% CI 1.70-9.03), and nonthyroid endocrine cancer (HR 7.49, 95% CI 4.47-12.56), endometrial (HR 8.32, 95% CI 4.22-16.40), ovarian (HR 4.00, 95% CI 1.60-10.01), and nonmelanoma skin cancer (HR 3.27, 95% CI 1.32-8.13).\n\nHere, we analyze the cancer risk spectrum of patients with muscular dystrophy and myotonic dystrophy. To the best of our knowledge, this is the first report of an increased risk for CNS tumors in childhood and adult nonthyroid endocrine and pancreatic cancer in muscular dystrophy. Furthermore, for myotonic dystrophy, we confirmed previously reported associations with cancer and expanded the cancer spectrum, finding an unreported increased risk for nonthyroid endocrine cancer. Additional studies confirming the cancer risk and delineating the cancer spectrum in different genetic subtypes of muscular dystrophies are warranted before considering altered cancer screening recommendations than for the general population.", "doi": "10.1212/WNL.0000000000209883", "pmid": "39298705", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11446166"}], "notes": [], "created": "2024-11-25T16:59:48.241Z", "modified": "2024-11-25T16:59:48.673Z"}, {"entity": "publication", "iuid": "4bc7ec8ead1d4139bf2d4017afe1bd61", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4bc7ec8ead1d4139bf2d4017afe1bd61.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4bc7ec8ead1d4139bf2d4017afe1bd61"}}, "title": "Clinical, genetic and structural delineation of RPL13-related spondyloepimetaphyseal dysplasia suggest extra-ribosomal functions of eL13.", "authors": [{"family": "Jacob", "given": "Prince", "initials": "P", "orcid": "0000-0002-3343-3262", "researcher": {"href": "https://publications.scilifelab.se/researcher/e996caa7e6914b379208eb78bff9745b.json"}}, {"family": "Lindel\u00f6f", "given": "Hillevi", "initials": "H"}, {"family": "Rustad", "given": "Cecilie F", "initials": "CF", "orcid": "0000-0001-7903-9087", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a07a4976faf41e0a32c6f6183b2c4b0.json"}}, {"family": "Sutton", "given": "Vernon Reid", "initials": "VR"}, {"family": "Moosa", "given": "Shahida", "initials": "S"}, {"family": "Udupa", "given": "Prajna", "initials": "P"}, {"family": "Hammarsj\u00f6", "given": "Anna", "initials": "A"}, {"family": "Bhavani", "given": "Gandham SriLakshmi", "initials": "GS"}, {"family": "Batkovskyte", "given": "Dominyka", "initials": "D", "orcid": "0000-0002-0492-1259", "researcher": {"href": "https://publications.scilifelab.se/researcher/017749b78ac540a6b2a36303130606f2.json"}}, {"family": "Tveten", "given": "Kristian", "initials": "K"}, {"family": "Dalal", "given": "Ashwin", "initials": "A"}, {"family": "Horemuzova", "given": "Eva", "initials": "E"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Tham", "given": "Emma", "initials": "E"}, {"family": "Shah", "given": "Hitesh", "initials": "H"}, {"family": "Merckoll", "given": "Else", "initials": "E"}, {"family": "Orellana", "given": "Laura", "initials": "L"}, {"family": "Nishimura", "given": "Gen", "initials": "G"}, {"family": "Girisha", "given": "Katta M", "initials": "KM", "orcid": "0000-0002-0139-8239", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e2ed42024554f40a944c4d507a6cabe.json"}}, {"family": "Grigelioniene", "given": "Giedre", "initials": "G"}], "type": "journal article", "published": "2023-11-22", "journal": {"title": "npj Genom. Med.", "issn": "2056-7944", "volume": "8", "issue": "1", "pages": "39", "issn-l": "2056-7944"}, "abstract": "Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2-64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, retaining the same radiographic pattern of spondylar- and epi-metaphyseal dysplasia, but with varying severity of the hip and knee deformities. Two new missense variants, c.548 G>A, p.(Arg183His) and c.569 G>T, p.(Arg190Leu), and a previously known splice variant c.477+1G>A were identified, confirming mutational clustering in a highly specific RNA binding motif. Structural analysis and interpretation of the variants' impact on the protein suggests that disruption of extra-ribosomal functions of the protein through binding of mRNA may play a role in the skeletal phenotype of SEMD-RPL13. In addition, we present gonadal and somatic mosaicism for the condition.", "doi": "10.1038/s41525-023-00380-x", "pmid": "37993442", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10665555"}, {"db": "pii", "key": "10.1038/s41525-023-00380-x"}], "notes": [], "created": "2023-12-04T11:30:28.842Z", "modified": "2024-11-28T18:27:37.037Z"}, {"entity": "publication", "iuid": "cd448ce0b19746f38c1fe9249ff70662", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cd448ce0b19746f38c1fe9249ff70662.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cd448ce0b19746f38c1fe9249ff70662"}}, "title": "Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer.", "authors": [{"family": "Wadensten", "given": "Elisabeth", "initials": "E"}, {"family": "Wessman", "given": "Sandra", "initials": "S", "orcid": "0000-0002-2035-2092", "researcher": {"href": "https://publications.scilifelab.se/researcher/f4680125750b4d949d691a745818a6f7.json"}}, {"family": "Abel", "given": "Frida", "initials": "F", "orcid": "0000-0001-6958-4487", "researcher": {"href": "https://publications.scilifelab.se/researcher/957445dd84024bac8cc6b1cca2f07473.json"}}, {"family": "Diaz De St\u00e5hl", "given": "Teresita", "initials": "T", "orcid": "0000-0001-5933-6623", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f51158ce6e14f3b96bf16a214689d1d.json"}}, {"family": "Tesi", "given": "Bianca", "initials": "B"}, {"family": "Orsmark Pietras", "given": "Christina", "initials": "C"}, {"family": "Arvidsson", "given": "Linda", "initials": "L"}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Fransson", "given": "Susanne", "initials": "S", "orcid": "0000-0002-9713-3074", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3f155163dae47478aae39b9c47fdadc.json"}}, {"family": "Vogt", "given": "Hartmut", "initials": "H", "orcid": "0000-0001-6009-7789", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e08eceec8ff418a961e32d0518ab97a.json"}}, {"family": "Poluha", "given": "Anna", "initials": "A", "orcid": "0000-0002-4716-9423", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7c9d843ebd549a7875bf10d4a16ee8b.json"}}, {"family": "Pradhananga", "given": "Sailendra", "initials": "S"}, {"family": "Hellberg", "given": "Maria", "initials": "M"}, {"family": "Lagerstedt-Robinson", "given": "Kristina", "initials": "K"}, {"family": "Raj Somarajan", "given": "Praveen", "initials": "P", "orcid": "0009-0005-5981-2286", "researcher": {"href": "https://publications.scilifelab.se/researcher/00a17539de3840108fa5d4bb9f454bab.json"}}, {"family": "Samuelsson", "given": "Sofie", "initials": "S"}, {"family": "Orrsj\u00f6", "given": "Sara", "initials": "S", "orcid": "0009-0008-9223-3923", "researcher": {"href": "https://publications.scilifelab.se/researcher/acd6e5385a7b4406b973a3adbed96245.json"}}, {"family": "Maqbool", "given": "Khurram", "initials": "K", "orcid": "0000-0003-2981-2582", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ea06b85057744018f754c373fef3ca5.json"}}, {"family": "Henning", "given": "Karin", "initials": "K"}, {"family": "Strid", "given": "Tobias", "initials": "T"}, {"family": "Ek", "given": "Torben", "initials": "T", "orcid": "0000-0002-0518-983X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce340b203a7840b786b73fb94c12c49a.json"}}, {"family": "Fagman", "given": "Henrik", "initials": "H"}, {"family": "Olsson Bontell", "given": "Thomas", "initials": "T"}, {"family": "Martinsson", "given": "Tommy", "initials": "T", "orcid": "0000-0002-9403-3123", "researcher": {"href": "https://publications.scilifelab.se/researcher/90deb3f5dd5446e5853da797411dfd5d.json"}}, {"family": "Puls", "given": "Florian", "initials": "F", "orcid": "0000-0002-9841-4230", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb2d41b4d47c41e89d675a438efd9095.json"}}, {"family": "Kogner", "given": "Per", "initials": "P", "orcid": "0000-0002-2202-9694", "researcher": {"href": "https://publications.scilifelab.se/researcher/e963274b921a4a2c8263f509334d4e22.json"}}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Pronk", "given": "Cornelis Jan", "initials": "CJ", "orcid": "0000-0002-0073-9660", "researcher": {"href": "https://publications.scilifelab.se/researcher/76e42ba48d824aa0b42e871e9f11b00a.json"}}, {"family": "Wille", "given": "Joakim", "initials": "J", "orcid": "0009-0008-6426-9830", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b06137add284e3ca519eb0af7bf52d4.json"}}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications.scilifelab.se/researcher/b570128e641140fb964ae3241414f510.json"}}, {"family": "Nist\u00e9r", "given": "Monica", "initials": "M", "orcid": "0000-0002-1261-3790", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1dc80e61f574293a190f2f3ef464988.json"}}, {"family": "Mertens", "given": "Fredrik", "initials": "F"}, {"family": "Sabel", "given": "Magnus", "initials": "M", "orcid": "0000-0002-3072-657X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2378bd05915d47eca234fff49fb69289.json"}}, {"family": "Nor\u00e9n-Nystr\u00f6m", "given": "Ulrika", "initials": "U", "orcid": "0000-0001-5606-5442", "researcher": {"href": "https://publications.scilifelab.se/researcher/03f7a89bc35d4e72b4b2c0d4252b69f0.json"}}, {"family": "Grillner", "given": "Pernilla", "initials": "P"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Ljungman", "given": "Gustaf", "initials": "G"}, {"family": "Sandgren", "given": "Johanna", "initials": "J", "orcid": "0000-0001-6776-2649", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d5b6b16fdbe470f83de8748227f8987.json"}}, {"family": "Gisselsson", "given": "David", "initials": "D", "orcid": "0000-0002-0301-426X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3653582762b14f9a9ad2fe6aba511115.json"}}, {"family": "Genomic Medicine Sweden Childhood Cancer Working Group", "given": "", "initials": ""}], "type": "journal article", "published": "2023-06-00", "journal": {"title": "JCO Precision Oncology", "issn": "2473-4284", "issn-l": "2473-4284", "volume": "7", "issue": null, "pages": "e2300039"}, "abstract": "Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.\n\nWe implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.\n\nDuring the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).\n\nUp-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.", "doi": "10.1200/PO.23.00039", "pmid": "37384868", "labels": {"NGI Short read": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Stockholm (Genomics Production)": "Collaborative", "Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10581599"}], "notes": [], "created": "2023-10-11T08:39:38.509Z", "modified": "2024-11-21T07:53:59.877Z"}, {"entity": "publication", "iuid": "8f99faf4497b42b4bf664ee35621c290", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8f99faf4497b42b4bf664ee35621c290.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8f99faf4497b42b4bf664ee35621c290"}}, "title": "Implementing precision medicine in a regionally organized healthcare system in Sweden.", "authors": [{"family": "Fioretos", "given": "Thoas", "initials": "T"}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Cavelier", "given": "Lucia", "initials": "L"}, {"family": "Berglund", "given": "Eva", "initials": "E"}, {"family": "Friedman", "given": "Mikaela", "initials": "M", "orcid": "0000-0002-5483-9771", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1507c81499748d8bf0ee1eb647a37d4.json"}}, {"family": "Akhras", "given": "Michael", "initials": "M"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Ehrencrona", "given": "Hans", "initials": "H", "orcid": "0000-0002-5589-3622", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b89608a8ce941c3b9911630b4ff9720.json"}}, {"family": "Engstrand", "given": "Lars", "initials": "L"}, {"family": "Helenius", "given": "Gisela", "initials": "G"}, {"family": "Fagerqvist", "given": "Therese", "initials": "T"}, {"family": "Gisselsson", "given": "David", "initials": "D", "orcid": "0000-0002-0301-426X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3653582762b14f9a9ad2fe6aba511115.json"}}, {"family": "Gruvberger-Saal", "given": "Sofia", "initials": "S", "orcid": "0000-0002-8478-9920", "researcher": {"href": "https://publications.scilifelab.se/researcher/70ffd3b67d32420e841027d5ff630b4c.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U", "orcid": "0000-0002-6316-3355", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8739f0f42c44019ab88a49db350a4f2.json"}}, {"family": "Heidenblad", "given": "Markus", "initials": "M", "orcid": "0000-0002-0668-2263", "researcher": {"href": "https://publications.scilifelab.se/researcher/b49a0816fc794c27a25b34731e8ca7bf.json"}}, {"family": "H\u00f6glund", "given": "Kina", "initials": "K"}, {"family": "Jacobsson", "given": "Bo", "initials": "B", "orcid": "0000-0001-5079-2374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd6968816ded4a50b1029ee3f4afbeed.json"}}, {"family": "Johansson", "given": "Maria", "initials": "M"}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5", "orcid": "0000-0002-2915-4498", "researcher": {"href": "https://publications.scilifelab.se/researcher/76265c54961046e99bdb0439f9ae1d34.json"}}, {"family": "Soller", "given": "Maria Johansson", "initials": "MJ"}, {"family": "Landstr\u00f6m", "given": "Mar\u00e9ne", "initials": "M", "orcid": "0000-0001-6737-7230", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2f02fcfb1c1497d81a6f343bc0e6928.json"}}, {"family": "Larsson", "given": "P\u00e4r", "initials": "P"}, {"family": "Levin", "given": "Lars-\u00c5ke", "initials": "L"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Lovmar", "given": "Lovisa", "initials": "L"}, {"family": "Lyander", "given": "Anna", "initials": "A"}, {"family": "Melin", "given": "Malin", "initials": "M"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Nordmark", "given": "Gunnel", "initials": "G", "orcid": "0000-0002-3829-7431", "researcher": {"href": "https://publications.scilifelab.se/researcher/188fda53498740dbb007441cc94bb1ad.json"}}, {"family": "M\u00f6lling", "given": "Paula", "initials": "P"}, {"family": "Palmqvist", "given": "Lars", "initials": "L", "orcid": "0000-0001-9274-360X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e50c0057dcb47f39e085b16580806c2.json"}}, {"family": "Palmqvist", "given": "Richard", "initials": "R"}, {"family": "Repsilber", "given": "Dirk", "initials": "D"}, {"family": "Sikora", "given": "Per", "initials": "P"}, {"family": "Stenmark", "given": "Bianca", "initials": "B"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P", "orcid": "0000-0001-9867-8706", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fc163b9a08421180f7f235af3897f4.json"}}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}, {"family": "Strid", "given": "Tobias", "initials": "T"}, {"family": "Wheelock", "given": "Craig E", "initials": "CE", "orcid": "0000-0002-8113-0653", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3cd2b99e3e9486ba41030c809a48c51.json"}}, {"family": "Wadelius", "given": "Mia", "initials": "M", "orcid": "0000-0002-6368-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec07b9869a1f4b77b734c5dc567dc630.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Edsj\u00f6", "given": "Anders", "initials": "A"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "letter", "published": "2022-10-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "issn-l": "1078-8956", "volume": "28", "issue": "10", "pages": "1980-1982"}, "abstract": null, "doi": "10.1038/s41591-022-01963-4", "pmid": "36123428", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics Ume\u00e5": "Service", "Clinical Genomics Uppsala": "Collaborative", "Clinical Genomics Stockholm": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41591-022-01963-4"}], "notes": [], "created": "2022-12-01T14:09:51.971Z", "modified": "2023-11-22T21:50:50.052Z"}, {"entity": "publication", "iuid": "cf455f938530449ea97efa2baec43961", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cf455f938530449ea97efa2baec43961.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cf455f938530449ea97efa2baec43961"}}, "title": "High diagnostic yield in skeletal ciliopathies using massively parallel genome sequencing, structural variant screening and RNA analyses.", "authors": [{"family": "Hammarsj\u00f6", "given": "Anna", "initials": "A", "orcid": "0000-0001-6585-0944", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b111d2b20a447a88a3a95af425cf14.json"}}, {"family": "Pettersson", "given": "Maria", "initials": "M"}, {"family": "Chitayat", "given": "David", "initials": "D"}, {"family": "Handa", "given": "Atsuhiko", "initials": "A", "orcid": "0000-0001-6401-4629", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b3be1c4b2174983a06b8e69e339bca9.json"}}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Bartocci", "given": "Marco", "initials": "M"}, {"family": "Basel", "given": "Donald", "initials": "D"}, {"family": "Batkovskyte", "given": "Dominyka", "initials": "D"}, {"family": "Beleza-Meireles", "given": "Ana", "initials": "A"}, {"family": "Conner", "given": "Peter", "initials": "P"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Girisha", "given": "Katta M", "initials": "KM"}, {"family": "Chung", "given": "Brian Hon-Yin", "initials": "BH", "orcid": "0000-0002-7044-5916", "researcher": {"href": "https://publications.scilifelab.se/researcher/73f2da34809a40ffbbc77e47e786baa2.json"}}, {"family": "Horemuzova", "given": "Eva", "initials": "E"}, {"family": "Hyodo", "given": "Hironobu", "initials": "H", "orcid": "0000-0002-1859-7525", "researcher": {"href": "https://publications.scilifelab.se/researcher/f4cacab0283346f083200ac21d749de6.json"}}, {"family": "Kor\u0146ejeva", "given": "Liene", "initials": "L"}, {"family": "Lagerstedt-Robinson", "given": "Kristina", "initials": "K", "orcid": "0000-0001-9848-0468", "researcher": {"href": "https://publications.scilifelab.se/researcher/63d275105d9b4253944abaa311c986ee.json"}}, {"family": "Lin", "given": "Angela E", "initials": "AE"}, {"family": "Magnusson", "given": "M\u00e5ns", "initials": "M"}, {"family": "Moosa", "given": "Shahida", "initials": "S"}, {"family": "Nayak", "given": "Shalini S", "initials": "SS"}, {"family": "Nilsson", "given": "Daniel", "initials": "D"}, {"family": "Ohashi", "given": "Hirofumi", "initials": "H"}, {"family": "Ohashi-Fukuda", "given": "Naoko", "initials": "N"}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Traberg", "given": "Rasa", "initials": "R"}, {"family": "Voss", "given": "Ulrika", "initials": "U"}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Nishimura", "given": "Gen", "initials": "G"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Grigelioniene", "given": "Giedre", "initials": "G", "orcid": "0000-0001-9601-3137", "researcher": {"href": "https://publications.scilifelab.se/researcher/684864357acd490cb627f38fed3b82a4.json"}}], "type": "journal article", "published": "2021-10-00", "journal": {"title": "J. Hum. Genet.", "issn": "1435-232X", "volume": "66", "issue": "10", "pages": "995-1008", "issn-l": "1434-5161"}, "abstract": "Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia and internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, are reported to cause skeletal ciliopathies. Here, we summarize genetic and phenotypic features of 34 affected individuals from 29 families with skeletal ciliopathies. Molecular diagnostic testing was performed using massively parallel sequencing (MPS) in combination with copy number variant (CNV) analyses and in silico filtering for variants in known skeletal ciliopathy genes. We identified biallelic disease-causing variants in seven genes: DYNC2H1, KIAA0753, WDR19, C2CD3, TTC21B, EVC, and EVC2. Four variants located in non-canonical splice sites of DYNC2H1, EVC, and KIAA0753 led to aberrant splicing that was shown by sequencing of cDNA. Furthermore, CNV analyses showed an intragenic deletion of DYNC2H1 in one individual and a 6.7 Mb de novo deletion on chromosome 1q24q25 in another. In five unsolved cases, MPS was performed in family setting. In one proband we identified a de novo variant in PRKACA and in another we found a homozygous intragenic deletion of IFT74, removing the first coding exon and leading to expression of a shorter message predicted to result in loss of 40 amino acids at the N-terminus. These findings establish IFT74 as a new skeletal ciliopathy gene. In conclusion, combined single nucleotide variant, CNV and cDNA analyses lead to a high yield of genetic diagnoses (90%) in a cohort of patients with skeletal ciliopathies.", "doi": "10.1038/s10038-021-00925-x", "pmid": "33875766", "labels": {"Clinical Genomics Stockholm": "Service", "NGI Stockholm (Genomics Production)": null, "NGI Stockholm (Genomics Applications)": null, "National Genomics Infrastructure": null, "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s10038-021-00925-x"}, {"db": "pmc", "key": "PMC8472897"}], "notes": [], "created": "2021-04-26T21:54:07.828Z", "modified": "2024-01-16T13:48:38.399Z"}, {"entity": "publication", "iuid": "d9786edd8d5e4150b3faa03d68d049c6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d9786edd8d5e4150b3faa03d68d049c6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d9786edd8d5e4150b3faa03d68d049c6"}}, "title": "A complex DICER1 syndrome phenotype associated with a germline pathogenic variant affecting the RNase IIIa domain of DICER1.", "authors": [{"family": "Pont\u00e9n", "given": "Emeli", "initials": "E", "orcid": "0000-0002-9174-9804", "researcher": {"href": "https://publications.scilifelab.se/researcher/44288e8f9187470d9def77dada73694a.json"}}, {"family": "Frisk", "given": "Sofia", "initials": "S"}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Vaz", "given": "Raquel", "initials": "R"}, {"family": "Wessman", "given": "Sandra", "initials": "S"}, {"family": "de Kock", "given": "Leanne", "initials": "L", "orcid": "0000-0001-7314-1371", "researcher": {"href": "https://publications.scilifelab.se/researcher/60d4da1ea1ab4784bb227d5702e7584a.json"}}, {"family": "Pal", "given": "Niklas", "initials": "N"}, {"family": "Foulkes", "given": "William D", "initials": "WD", "orcid": "0000-0001-7427-4651", "researcher": {"href": "https://publications.scilifelab.se/researcher/2554bd69c2b44a3482ab0ce1df6e4eda.json"}}, {"family": "Lagerstedt-Robinson", "given": "Kristina", "initials": "K", "orcid": "0000-0001-9848-0468", "researcher": {"href": "https://publications.scilifelab.se/researcher/63d275105d9b4253944abaa311c986ee.json"}}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}], "type": "journal article", "published": "2020-11-18", "journal": {"title": "J. Med. Genet.", "issn": "1468-6244", "volume": null, "issue": null, "pages": "jmedgenet-2020-107385", "issn-l": "0022-2593"}, "abstract": "Germline pathogenic variants in DICER1 cause DICER1 syndrome, an autosomal dominant, pleiotropic tumour predisposition syndrome with variable expressivity and reduced penetrance for specific dysplastic and neoplastic lesions. Recently, a syndrome with the acronym GLOW (Global developmental delay, Lung cysts, Overgrowth, Wilms tumour) was described in two children with mosaic missense mutations in hotspot residues of the DICER1 RNase IIIb domain.\n\nWhole genome sequencing, exome sequencing, Sanger sequencing, digital PCR and a review of Wilms tumours with DICER1 RNase III domain mutations were performed.\n\nA de novo heterozygous c.4031C>T (p.S1344L) variant in the sequence encoding the RNase IIIa domain of DICER1 was detected. Clinical investigations revealed a phenotype that resembles the GLOW subphenotype of DICER1 syndrome.\n\nThe phenotypic overlap between patients with p.S1344L mutation and GLOW syndrome provide clinical support for recent discoveries that RNase IIIa-Ser1344 site mutations impede miRNA-5p biogenesis analogous to DICER1 hotspot mutations in the RNase IIIb domain. We show that an individual with a heterozygous germline p.S1344L mutation has a severe form of DICER1 syndrome ('DICER1 syndrome plus'), with notable features of intellectual disability, macrocephaly, physical abnormalities, Wilms tumour and a well-differentiated fetal adenocarcinoma of the lung.", "doi": "10.1136/jmedgenet-2020-107385", "pmid": "33208384", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "jmedgenet-2020-107385"}], "notes": [], "created": "2020-11-23T08:05:52.969Z", "modified": "2021-11-20T12:18:57.716Z"}, {"entity": "publication", "iuid": "c4ca7ddb792e49aab70137c27e6970f3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c4ca7ddb792e49aab70137c27e6970f3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c4ca7ddb792e49aab70137c27e6970f3"}}, "title": "Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.", "authors": [{"family": "Wang", "given": "Tianyun", "initials": "T", "orcid": "0000-0002-5179-087X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f8343adbdf84296a4bf04c6890d49d2.json"}}, {"family": "Hoekzema", "given": "Kendra", "initials": "K"}, {"family": "Vecchio", "given": "Davide", "initials": "D", "orcid": "0000-0003-2907-3206", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7d64eefa6a041caad3a8c860e76d84e.json"}}, {"family": "Wu", "given": "Huidan", "initials": "H"}, {"family": "Sulovari", "given": "Arvis", "initials": "A", "orcid": "0000-0003-4354-9020", "researcher": {"href": "https://publications.scilifelab.se/researcher/85f6043d9c7c4ca49ced9ed1c0f97340.json"}}, {"family": "Coe", "given": "Bradley P", "initials": "BP"}, {"family": "Gillentine", "given": "Madelyn A", "initials": "MA", "orcid": "0000-0002-8989-2214", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e5086e94ffb4bc7a8367b15d17b876e.json"}}, {"family": "Wilfert", "given": "Amy B", "initials": "AB"}, {"family": "Perez-Jurado", "given": "Luis A", "initials": "LA"}, {"family": "Kvarnung", "given": "Malin", "initials": "M"}, {"family": "Sleyp", "given": "Yoeri", "initials": "Y"}, {"family": "Earl", "given": "Rachel K", "initials": "RK"}, {"family": "Rosenfeld", "given": "Jill A", "initials": "JA", "orcid": "0000-0001-5664-7987", "researcher": {"href": "https://publications.scilifelab.se/researcher/1826b4a473304149a22a9646d6f76a3e.json"}}, {"family": "Geisheker", "given": "Madeleine R", "initials": "MR", "orcid": "0000-0002-4166-3236", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3494f8f657c4d0fbbd886ac89ac9cfa.json"}}, {"family": "Han", "given": "Lin", "initials": "L"}, {"family": "Du", "given": "Bing", "initials": "B"}, {"family": "Barnett", "given": "Chris", "initials": "C"}, {"family": "Thompson", "given": "Elizabeth", "initials": "E"}, {"family": "Shaw", "given": "Marie", "initials": "M"}, {"family": "Carroll", "given": "Renee", "initials": "R"}, {"family": "Friend", "given": "Kathryn", "initials": "K"}, {"family": "Catford", "given": "Rachael", "initials": "R"}, {"family": "Palmer", "given": "Elizabeth E", "initials": "EE"}, {"family": "Zou", "given": "Xiaobing", "initials": "X"}, {"family": "Ou", "given": "Jianjun", "initials": "J"}, {"family": "Li", "given": "Honghui", "initials": "H"}, {"family": "Guo", "given": "Hui", "initials": "H", "orcid": "0000-0002-1570-2545", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b7e6c55e24449fd9b53f6ed08003742.json"}}, {"family": "Gerdts", "given": "Jennifer", "initials": "J"}, {"family": "Avola", "given": "Emanuela", "initials": "E"}, {"family": "Calabrese", "given": "Giuseppe", "initials": "G"}, {"family": "Elia", "given": "Maurizio", "initials": "M"}, {"family": "Greco", "given": "Donatella", "initials": "D"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Vandeweyer", "given": "Geert", "initials": "G"}, {"family": "Van Dijck", "given": "Anke", "initials": "A", "orcid": "0000-0002-6713-2943", "researcher": {"href": "https://publications.scilifelab.se/researcher/b190da43c29e4245b71b37ab7cdb81db.json"}}, {"family": "Van der Aa", "given": "Nathalie", "initials": "N"}, {"family": "McKenna", "given": "Brooke", "initials": "B"}, {"family": "Hancarova", "given": "Miroslava", "initials": "M"}, {"family": "Bendova", "given": "Sarka", "initials": "S"}, {"family": "Havlovicova", "given": "Marketa", "initials": "M"}, {"family": "Malerba", "given": "Giovanni", "initials": "G"}, {"family": "Bernardina", "given": "Bernardo Dalla", "initials": "BD"}, {"family": "Muglia", "given": "Pierandrea", "initials": "P"}, {"family": "van Haeringen", "given": "Arie", "initials": "A"}, {"family": "Hoffer", "given": "Mariette J V", "initials": "MJV", "orcid": "0000-0002-1812-7670", "researcher": {"href": "https://publications.scilifelab.se/researcher/04747e9661474d43a1f4a7ed51eb7207.json"}}, {"family": "Franke", "given": "Barbara", "initials": "B", "orcid": "0000-0003-4375-6572", "researcher": {"href": "https://publications.scilifelab.se/researcher/105f0131cfc34a668ed840e622e4f902.json"}}, {"family": "Cappuccio", "given": "Gerarda", "initials": "G"}, {"family": "Delatycki", "given": "Martin", "initials": "M"}, {"family": "Lockhart", "given": "Paul J", "initials": "PJ", "orcid": "0000-0003-2531-8413", "researcher": {"href": "https://publications.scilifelab.se/researcher/af606d21d6524fbdbd65f044fddbd00b.json"}}, {"family": "Manning", "given": "Melanie A", "initials": "MA"}, {"family": "Liu", "given": "Pengfei", "initials": "P", "orcid": "0000-0002-4177-709X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8bda9fff7cc042eaa054b5257799c1f4.json"}}, {"family": "Scheffer", "given": "Ingrid E", "initials": "IE"}, {"family": "Brunetti-Pierri", "given": "Nicola", "initials": "N", "orcid": "0000-0002-6895-8819", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9785f9985d645259283e808cdcd77a9.json"}}, {"family": "Rommelse", "given": "Nanda", "initials": "N"}, {"family": "Amaral", "given": "David G", "initials": "DG"}, {"family": "Santen", "given": "Gijs W E", "initials": "GWE"}, {"family": "Trabetti", "given": "Elisabetta", "initials": "E"}, {"family": "Sedl\u00e1\u010dek", "given": "Zden\u011bk", "initials": "Z"}, {"family": "Michaelson", "given": "Jacob J", "initials": "JJ", "orcid": "0000-0001-9713-0992", "researcher": {"href": "https://publications.scilifelab.se/researcher/13cd0bf6a3c3437485c0c8c6a32839dc.json"}}, {"family": "Pierce", "given": "Karen", "initials": "K"}, {"family": "Courchesne", "given": "Eric", "initials": "E", "orcid": "0000-0002-3772-5799", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae6305c8ed044e1ca6b637f982d181c4.json"}}, {"family": "Kooy", "given": "R Frank", "initials": "RF", "orcid": "0000-0003-2024-0485", "researcher": {"href": "https://publications.scilifelab.se/researcher/d0e9d246a6ac47029258886b9537a0e5.json"}}, {"family": "SPARK Consortium", "given": "", "initials": ""}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Romano", "given": "Corrado", "initials": "C", "orcid": "0000-0003-1049-0683", "researcher": {"href": "https://publications.scilifelab.se/researcher/634b98b512e84042af68e05eff055978.json"}}, {"family": "Peeters", "given": "Hilde", "initials": "H"}, {"family": "Bernier", "given": "Raphael A", "initials": "RA"}, {"family": "Gecz", "given": "Jozef", "initials": "J", "orcid": "0000-0002-7884-6861", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfa0d2adb36840858e1f9f8e407269b0.json"}}, {"family": "Xia", "given": "Kun", "initials": "K", "orcid": "0000-0001-8090-6002", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbfe349e05c740a7894d1bab511a3768.json"}}, {"family": "Eichler", "given": "Evan E", "initials": "EE", "orcid": "0000-0002-8246-4014", "researcher": {"href": "https://publications.scilifelab.se/researcher/43901cc9fc3b4f5c9a18260e36558eb9.json"}}], "type": "journal article", "published": "2020-10-01", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4932", "issn-l": "2041-1723"}, "abstract": "Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.", "doi": "10.1038/s41467-020-18723-y", "pmid": "33004838", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-18723-y"}, {"db": "pmc", "key": "PMC7530681"}], "notes": [], "created": "2021-11-20T12:18:30.540Z", "modified": "2021-11-20T12:18:31.111Z"}, {"entity": "publication", "iuid": "804fe367d4ba45b59d3d3ed95177e766", "links": {"self": {"href": "https://publications.scilifelab.se/publication/804fe367d4ba45b59d3d3ed95177e766.json"}, "display": {"href": "https://publications.scilifelab.se/publication/804fe367d4ba45b59d3d3ed95177e766"}}, "title": "Overexpression of chromatin remodeling and tyrosine kinase genes in iAMP21-positive acute lymphoblastic leukemia.", "authors": [{"family": "Ivanov \u00d6fverholm", "given": "Ingegerd", "initials": "I", "orcid": "0000-0002-6907-8004", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ba94eeea4d24e9c8c354fe1256fd0ce.json"}}, {"family": "Zachariadis", "given": "Vasilios", "initials": "V", "orcid": "0000-0001-9360-9859", "researcher": {"href": "https://publications.scilifelab.se/researcher/0607f2b65c12492cb30fb7a445d37937.json"}}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Marincevic-Zuniga", "given": "Yanara", "initials": "Y", "orcid": "0000-0001-5576-2115", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb045b70f16140b6b6e69476d701012c.json"}}, {"family": "Tran", "given": "Anh Nhi", "initials": "AN"}, {"family": "Saft", "given": "Leonie", "initials": "L"}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "L\u00f6nnerholm", "given": "Gudmar", "initials": "G"}, {"family": "Harila-Saari", "given": "Arja", "initials": "A"}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M", "orcid": "0000-0002-4974-425X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9f9dec008f1b42868dd133e9a396c968.json"}}, {"family": "Heyman", "given": "Mats", "initials": "M"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Barbany", "given": "Gisela", "initials": "G"}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Leuk. Lymphoma", "issn": "1029-2403", "issn-l": "1026-8022", "volume": "61", "issue": "3", "pages": "604-613"}, "abstract": "Intrachromosomal amplification of chromosome 21 (iAMP21) is a cytogenetic subtype associated with relapse and poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). The biology behind the high relapse risk is unknown and the aim of this study was to further characterize the genomic and transcriptional landscape of iAMP21. Using DNA arrays and sequencing, we could identify rearrangements and aberrations characteristic for iAMP21. RNA sequencing revealed that only half of the genes in the minimal region of amplification (20/45) were differentially expressed in iAMP21. Among them were the top overexpressed genes (p < 0.001) in iAMP21 vs. BCP ALL without iAMP21 and three candidate genes could be identified, the tyrosine kinase gene DYRK1A and chromatin remodeling genes CHAF1B and SON. While overexpression of DYRK1A and CHAF1B is associated with poor prognosis in malignant diseases including myeloid leukemia, this is the first study to show significant correlation with iAMP21-positive ALL.", "doi": "10.1080/10428194.2019.1678153", "pmid": "31640433", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2019-12-03T10:45:21.445Z", "modified": "2024-01-16T13:48:42.841Z"}]}