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Most commonly, it is caused by autosomal dominant variants in the type I collagen genes, <jats:italic>COL1A1<\/jats:italic> or <jats:italic>COL1A2<\/jats:italic>. Type I collagen is the main protein of the extracellular matrix in the skeleton and changes in its structure or quantity may lead to OI. 85%\u201390% of OI cases occur due to sequence variants in type I collagen genes, while OI caused by structural abnormalities in type I collagen genes is less common. In most cases, haploinsufficiency of type I collagen is associated with a milder OI phenotype. Large genomic deletions often involve several genes within the same chromosomal region, leading to microdeletion syndromes with OI features. Here, we report eight Swedish patients from five unrelated families with OI due to structural variants in the <jats:italic>COL1A1<\/jats:italic> and <jats:italic>COL1A2<\/jats:italic> genes. One patient with OI type III had a complex rearrangement with a deletion and duplication event in <jats:italic>COL1A2<\/jats:italic>, leading to reduced COL1A2 expression. Three other patients from two different families with OI type I had whole gene deletions involving <jats:italic>COL1A1<\/jats:italic>. In one family, three affected individuals with OI type I had a small intragenic deletion of exons 11\u201312 in <jats:italic>COL1A2<\/jats:italic>. One patient had a 2.1\u2009Mb <jats:italic>de novo<\/jats:italic> deletion encompassing <jats:italic>COL1A1<\/jats:italic> and <jats:italic>DLX3<\/jats:italic> genes and features of OI and tricho\u2010dento\u2010osseous syndrome. Overall, this study highlights the importance of investigating gene dosage abnormalities in patients with OI and further delineates clinical and genetic variability of OI caused by structural variants in type I collagen genes.<\/jats:p>","DOI":"10.1002\/ajmg.a.63935","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T11:39:32Z","timestamp":1731065972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Structural Variants in <scp><i>COL1A1<\/i><\/scp> and <scp><i>COL1A2<\/i><\/scp> in Osteogenesis Imperfecta"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0492-1259","authenticated-orcid":false,"given":"Dominyka","family":"Batkovskyte","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Surgery and Center for Molecular Medicine Karolinska Institutet  Stockholm 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