{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:03:19Z","timestamp":1787580199532,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,22]],"date-time":"2024-12-22T00:00:00Z","timestamp":1734825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Osteogenesis imperfecta (OI) is a rare disease, hallmarked by bone fragility, multiple fractures, and deformities, and is commonly caused by pathogenic variants in the genes encoding type I collagen. Type II OI is the most severe form and is lethal in the perinatal period. Here, we report recurrence of perinatal lethal OI in two fetuses due to parental mosaicism for a deep intronic pathogenic variant at c.2451\u2009+\u200977C\u2009&gt;\u2009T in intron 35 of <jats:italic>COL1A1<\/jats:italic>, which resulted in aberrant splicing and the in\u2010frame addition of 75 nucleotides into the mRNA. These patients highlight the importance of considering deep intronic variants in type 1 collagen genes in patients with high suspicion of OI, which may be missed with conventional genetic analysis.<\/jats:p>","DOI":"10.1002\/ajmg.a.63972","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T07:30:00Z","timestamp":1734939000000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Deep Intronic Splice Variant in <i>COL1A1<\/i> Causing Osteogenesis Imperfecta Type <scp>II<\/scp>"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8874-9467","authenticated-orcid":false,"given":"Mackenna E.","family":"Schouw","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden The Netherlands"},{"name":"Department of Internal Medicine Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A. L.","family":"Ruivenkamp","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara T.","family":"Koopmann","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijs W. E.","family":"Santen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G. J.","family":"Nikkels","sequence":"additional","affiliation":[{"name":"Department of Pathology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"van der Tuin","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden The Netherlands"},{"name":"Department of Clinical Genetics University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina57050464"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2022.986372"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)00728\u2010X"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)60577-0"},{"key":"e_1_2_9_6_1","unstructured":"Leiden Open Variation Database.2024.\u201cThe COL1A1 Gene Homepage.\u201dhttps:\/\/databases.lovd.nl\/shared\/genes\/COL1A1."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00979"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.52"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20429"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genrep.2020.100803"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22812"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320170204"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.16.2.101"},{"key":"e_1_2_9_15_1","volume-title":"GeneReviews\u00ae","author":"Steiner R. 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