{"entity": "journal", "iuid": "011295d4390c4fe481564f1da9db9d49", "timestamp": "2026-07-22T17:36:29.518Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Orphanet%20J%20Rare%20Dis.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Orphanet%20J%20Rare%20Dis"}}, "title": "Orphanet J Rare Dis", "issn": "1750-1172", "issn-l": "1750-1172", "publications_count": 3, "publications": [{"entity": "publication", "iuid": "aa4c5877e251458ea28d7fc3e7c01791", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aa4c5877e251458ea28d7fc3e7c01791.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aa4c5877e251458ea28d7fc3e7c01791"}}, "title": "High content drug screening for Fanconi anemia therapeutics.", "authors": [{"family": "Montanuy", "given": "Helena", "initials": "H"}, {"family": "Camps-Fajol", "given": "Cristina", "initials": "C"}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Aza-Carmona", "given": "Miriam", "initials": "M"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Minguill\u00f3n", "given": "Jordi", "initials": "J"}, {"family": "Surrall\u00e9s", "given": "Jordi", "initials": "J"}], "type": "journal article", "published": "2020-06-30", "journal": {"title": "Orphanet J Rare Dis", "issn": "1750-1172", "volume": "15", "issue": "1", "pages": "170", "issn-l": "1750-1172"}, "abstract": "Fanconi anemia is a rare disease clinically characterized by malformations, bone marrow failure and an increased risk of solid tumors and hematologic malignancies. The only therapies available are hematopoietic stem cell transplantation for bone marrow failure or leukemia, and surgical resection for solid tumors. Therefore, there is still an urgent need for new therapeutic options. With this aim, we developed a novel high-content cell-based screening assay to identify drugs with therapeutic potential in FA.\n\nA TALEN-mediated FANCA-deficient U2OS cell line was stably transfected with YFP-FANCD2 fusion protein. These cells were unable to form fluorescent foci or to monoubiquitinate endogenous or exogenous FANCD2 upon DNA damage and were more sensitive to mitomycin C when compared to the parental wild type counterpart. FANCA correction by retroviral infection restored the cell line's ability to form FANCD2 foci and ubiquitinate FANCD2. The feasibility of this cell-based system was interrogated in a high content screening of 3802 compounds, including a Prestwick library of 1200 FDA-approved drugs. The potential hits identified were then individually tested for their ability to rescue FANCD2 foci and monoubiquitination, and chromosomal stability in the absence of FANCA.\n\nWhile, unfortunately, none of the compounds tested were able to restore cellular FANCA-deficiency, our study shows the potential capacity to screen large compound libraries in the context of Fanconi anemia therapeutics in an optimized and cost-effective platform.", "doi": "10.1186/s13023-020-01437-1", "pmid": "32605631", "labels": {"Drug Discovery and Development": null}, "xrefs": [{"db": "pii", "key": "10.1186/s13023-020-01437-1"}, {"db": "pmc", "key": "PMC7325660"}], "notes": [], "created": "2020-12-04T14:15:05.562Z", "modified": "2025-10-17T13:05:08.012Z"}, {"entity": "publication", "iuid": "ed38171ac9fb4267b06326f783d43541", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ed38171ac9fb4267b06326f783d43541.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ed38171ac9fb4267b06326f783d43541"}}, "title": "Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta.", "authors": [{"family": "Andersson", "given": "Kristofer", "initials": "K"}, {"family": "Malmgren", "given": "Barbro", "initials": "B"}, {"family": "\u00c5str\u00f6m", "given": "Eva", "initials": "E"}, {"family": "Nordgren", "given": "Ann", "initials": "A"}, {"family": "Taylan", "given": "Fulya", "initials": "F"}, {"family": "Dahll\u00f6f", "given": "G\u00f6ran", "initials": "G"}], "type": "journal article", "published": "2020-03-31", "journal": {"title": "Orphanet J Rare Dis", "issn": "1750-1172", "volume": "15", "issue": "1", "pages": "80", "issn-l": "1750-1172"}, "abstract": "Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by an increased tendency for fractures throughout life. Autosomal dominant (AD) mutations in COL1A1 and COL1A2 are causative in approximately 85% of cases. In recent years, recessive variants in genes involved in collagen processing have been found. Hypodontia (< 6 missing permanent teeth) and oligodontia (\u2265 6 missing permanent teeth) have previously been reported in individuals with OI. The aim of the present cross-sectional study was to investigate whether children and adolescents with OI and oligodontia and hypodontia also present with variants in other genes with potential effects on tooth development. The cohort comprised 10 individuals (7.7-19.9 years of age) with known COL1A1/A2 variants who we clinically and radiographically examined and further genetically evaluated by whole-genome sequencing. All study participants were treated at the Astrid Lindgren Children's Hospital at Karolinska University Hospital, Stockholm (Sweden's national multidisciplinary pediatric OI team). We evaluated a panel of genes that were associated with nonsyndromic and syndromic hypodontia or oligodontia as well as that had been found to be involved in tooth development in animal models.\n\nWe detected a homozygous nonsense variant in CREB3L1, p.Tyr428*, c.1284C > A in one boy previously diagnosed with OI type III. COL1A1 and COL1A2 were the only two genes among 9 individuals which carried a pathogenic mutation. We found rare variants with unknown significance in several other genes related to tooth development.\n\nOur findings suggest that mutations in COL1A1, COL1A2, and CREB3L1 may cause hypodontia and oligodontia in OI. The findings cannot exclude additive effects from other modifying or interacting genes that may contribute to the severity of the expressed phenotype. Larger cohorts and further functional studies are needed.", "doi": "10.1186/s13023-020-01361-4", "pmid": "32234057", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13023-020-01361-4"}, {"db": "pmc", "key": "PMC7110904"}], "notes": [], "created": "2020-07-08T13:04:37.345Z", "modified": "2021-11-10T12:52:44.175Z"}, {"entity": "publication", "iuid": "ef873ebb1c55436395968a885ee5232b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ef873ebb1c55436395968a885ee5232b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ef873ebb1c55436395968a885ee5232b"}}, "title": "Respiratory chain complex III deficiency due to mutated BCS1L: a novel phenotype with encephalomyopathy, partially phenocopied in a Bcs1l mutant mouse model.", "authors": [{"family": "Tegelberg", "given": "Saara", "initials": "S"}, {"family": "Toma\u0161i\u0107", "given": "Nikica", "initials": "N"}, {"family": "Kallij\u00e4rvi", "given": "Jukka", "initials": "J"}, {"family": "Purhonen", "given": "Janne", "initials": "J"}, {"family": "Elm\u00e9r", "given": "Eskil", "initials": "E"}, {"family": "Lindberg", "given": "Eva", "initials": "E"}, {"family": "Nord", "given": "David Gisselsson", "initials": "DG"}, {"family": "Soller", "given": "Maria", "initials": "M"}, {"family": "Lesko", "given": "Nicole", "initials": "N"}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Bruhn", "given": "Helene", "initials": "H"}, {"family": "Freyer", "given": "Christoph", "initials": "C"}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}, {"family": "Wibom", "given": "Rolf", "initials": "R"}, {"family": "Nennesmo", "given": "Inger", "initials": "I"}, {"family": "Wredenberg", "given": "Anna", "initials": "A"}, {"family": "Eklund", "given": "Erik A", "initials": "EA"}, {"family": "Fellman", "given": "Vineta", "initials": "V"}], "type": "journal article", "published": "2017-04-20", "journal": {"volume": "12", "issn": "1750-1172", "issue": "1", "pages": "73", "title": "Orphanet J Rare Dis", "issn-l": "1750-1172"}, "abstract": "Mitochondrial diseases due to defective respiratory chain complex III (CIII) are relatively uncommon. The assembly of the eleven-subunit CIII is completed by the insertion of the Rieske iron-sulfur protein, a process for which BCS1L protein is indispensable. Mutations in the BCS1L gene constitute the most common diagnosed cause of CIII deficiency, and the phenotypic spectrum arising from mutations in this gene is wide.\n\nA case of CIII deficiency was investigated in depth to assess respiratory chain function and assembly, and brain, skeletal muscle and liver histology. Exome sequencing was performed to search for the causative mutation(s). The patient's platelets and muscle mitochondria showed respiration defects and defective assembly of CIII was detected in fibroblast mitochondria. The patient was compound heterozygous for two novel mutations in BCS1L, c.306A\u2009>\u2009T and c.399delA. In the cerebral cortex a specific pattern of astrogliosis and widespread loss of microglia was observed. Further analysis showed loss of Kupffer cells in the liver. These changes were not found in infants suffering from GRACILE syndrome, the most severe BCS1L-related disorder causing early postnatal mortality, but were partially corroborated in a knock-in mouse model of BCS1L deficiency.\n\nWe describe two novel compound heterozygous mutations in BCS1L causing CIII deficiency. The pathogenicity of one of the mutations was unexpected and points to the importance of combining next generation sequencing with a biochemical approach when investigating these patients. We further show novel manifestations in brain, skeletal muscle and liver, including abnormality in specialized resident macrophages (microglia and Kupffer cells). These novel phenotypes forward our understanding of CIII deficiencies caused by BCS1L mutations.", "doi": "10.1186/s13023-017-0624-2", "pmid": "28427446", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13023-017-0624-2"}, {"db": "pmc", "key": "PMC5399415"}], "notes": [], "created": "2017-11-03T12:53:36.734Z", "modified": "2017-11-03T12:55:39.216Z"}], "created": "2017-11-03T12:53:36.750Z", "modified": "2020-11-27T13:14:06.801Z"}