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Oocytes require controlled DNA breakage and repair for homologous recombination and the maintenance of oocyte integrity. Biallelic disruption of the DNA damage repair gene, <jats:italic>Fanconi anemia complementation group A<\/jats:italic> (<jats:italic>FANCA)<\/jats:italic>, is a common cause of Fanconi anaemia, a syndrome characterised by bone marrow failure, cancer predisposition, physical anomalies and POI. There is ongoing dispute about the role of heterozygous <jats:italic>FANCA<\/jats:italic> variants in POI pathogenesis, with insufficient evidence supporting causation. Here, we have identified biallelic <jats:italic>FANCA<\/jats:italic> variants in French sisters presenting with POI, including a novel missense variant of uncertain significance and a likely pathogenic deletion that initially evaded detection. Functional studies indicated no discernible effect on DNA damage sensitivity in patient lymphoblasts. These novel <jats:italic>FANCA<\/jats:italic> variants add evidence that heterozygous loss of one allele is insufficient to cause DNA damage sensitivity and POI. We propose that intragenic deletions, that are relatively common in <jats:italic>FANCA<\/jats:italic>, may be missed without careful analysis, and could explain the presumed causation of heterozygous variants. Accurate variant curation is critical to optimise patient care and outcomes.<\/jats:p>","DOI":"10.1111\/cge.14543","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T08:05:00Z","timestamp":1716451500000},"page":"321-335","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Biallelic <i>FANCA<\/i> variants detected in sisters with isolated premature ovarian insufficiency"],"prefix":"10.1111","volume":"106","author":[{"given":"Elena J.","family":"Tucker","sequence":"first","affiliation":[{"name":"Reproductive Development Murdoch Children's Research Institute  Melbourne Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Sharp","sequence":"additional","affiliation":[{"name":"DNA Repair and Recombination Laboratory St. Vincent's Institute of 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S.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology and The Bio21 Molecular Science and Biotechnology Institute The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna L.","family":"Kline","sequence":"additional","affiliation":[{"name":"Reproductive Development Murdoch Children's Research Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorjana","family":"Robevska","sequence":"additional","affiliation":[{"name":"Reproductive Development Murdoch Children's Research Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"van den Bergen","sequence":"additional","affiliation":[{"name":"Reproductive Development Murdoch Children's Research Institute  Melbourne Victoria 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Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Touraine","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Reproductive Medicine, AP\u2010HP Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Crismani","sequence":"additional","affiliation":[{"name":"DNA Repair and Recombination Laboratory St. Vincent's Institute of Medical Research  Fitzroy Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Jaillard","sequence":"additional","affiliation":[{"name":"CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en sant\u00e9, environnement et travail) \u2010 UMR_S1085 Univ Rennes  Rennes France"},{"name":"Service de Cytog\u00e9n\u00e9tique et Biologie Cellulaire CHU Rennes  Rennes 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