{"entity": "researcher", "timestamp": "2026-07-22T17:14:41.658Z", "family": "Wincent", "given": "Josephine", "initials": "J", "orcid": "0000-0002-1698-9605", "affiliations": ["Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.", "Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/57e9777724444021924229d3fdc8673e.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/57e9777724444021924229d3fdc8673e"}}, "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": "9af4504b5bb14ae1a431ea29cee9c8d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9af4504b5bb14ae1a431ea29cee9c8d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9af4504b5bb14ae1a431ea29cee9c8d5"}}, "title": "Genome sequencing differentiates a paracentric inversion from a balanced insertion enabling more accurate preimplantation genetic testing.", "authors": [{"family": "Wincent", "given": "Josephine", "initials": "J", "orcid": "0000-0002-1698-9605", "researcher": {"href": "https://publications.scilifelab.se/researcher/57e9777724444021924229d3fdc8673e.json"}}, {"family": "Helgad\u00f3ttir", "given": "Hafd\u00eds T", "initials": "HT"}, {"family": "Sergouniotis", "given": "Fotios", "initials": "F"}, {"family": "Salazar Mantero", "given": "Angelo", "initials": "A"}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB"}, {"family": "Malmgren", "given": "Helena", "initials": "H"}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}, {"family": "Iwarsson", "given": "Erik", "initials": "E", "orcid": "0000-0002-3827-0263", "researcher": {"href": "https://publications.scilifelab.se/researcher/d626860f8ce14c6eaa79f9d1b7d76c0b.json"}}], "type": "journal article", "published": "2024-08-00", "journal": {"title": "Acta Obstet Gynecol Scand", "issn": "1600-0412", "volume": "103", "issue": "8", "pages": "1564-1569", "issn-l": "0001-6349"}, "abstract": "Distinguishing paracentric inversions (PAIs) from chromosomal insertions has traditionally relied on fluorescent in situ hybridization (FISH) techniques, but recent advancements in high-throughput sequencing have enabled the use of genome sequencing for such differentiation. In this study, we present a 38-year-old male carrier of a paracentric inversion on chromosome 2q, inv (2)(q31.2q34), whose partner experienced recurrent miscarriages.\n\nFISH analysis confirmed the inversion, and genome sequencing was employed for detailed characterization.\n\nPreimplantation genetic testing (PGT) revealed that all assessed embryos were balanced, consistent with the low risk of unbalanced offspring associated with PAIs. While PAI carriers traditionally exhibit low risk of producing unbalanced offspring, exceptions exist due to crossover events within the inversion loop. Although the sample size was limited, the findings align with existing sperm study data, supporting the rare occurrence of unbalanced progeny in PAI carriers.\n\nThis study highlights the possibility of characterizing PAIs using genome sequencing to enable correct reproductive counseling and PGT decisions. Detailed characterization of a PAI is crucial for understanding potential outcomes and guiding PGT strategies, as accurate knowledge of the inversion size is essential for appropriate method selection in PGT. Given the very low risk of unbalanced offspring in PAI carriers, routine PGT may not be warranted but should be considered in specific cases with a history of unbalanced progeny or recurrent miscarriages. This study contributes to our understanding of PAI segregation and its implications for reproductive outcomes.", "doi": "10.1111/aogs.14898", "pmid": "38872454", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11266630"}], "notes": [], "created": "2024-11-23T14:19:48.407Z", "modified": "2024-11-23T14:19:48.913Z"}]}