{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:48:18Z","timestamp":1792601298283,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/IN\/SWEDEN\/09\/VM\/2017"],"award-info":[{"award-number":["BT\/IN\/SWEDEN\/09\/VM\/2017"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["54\/9\/2015\u2010HUM\u2010BMS"],"award-info":[{"award-number":["54\/9\/2015\u2010HUM\u2010BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Heterozygous <jats:italic>COL1A1<\/jats:italic> and <jats:italic>COL1A2<\/jats:italic> gene variants are known to cause osteogenesis imperfecta (OI) in 90% of the patients in the Western and Japanese populations. Two previous Indian reports, a total of 49 patients, showed their proportion in the Indian population to be 44% and 71%. We studied a population of 210 children with a clinical diagnosis of OI and focused on the cohort of children with (likely) pathogenic <jats:italic>COL1A1\/COL1A2<\/jats:italic> variants. The prospective study describes the clinical, radiological, and genetic findings of 100 <jats:italic>COL1A1\/A2<\/jats:italic> variants. Phenotypic evaluation included the type of OI, fracture history, extraskeletal and skeletal features, pamidronate treatment, and its effect on bone density. Genotyping was assessed by clinical or targeted exome sequencing and validated by Sanger sequencing. One hundred patients, including affected siblings, out of 210 had <jats:italic>COL1A1\/A2<\/jats:italic> gene variants. No genetic cause was found in 25, and the remaining had causative variants in other OI\u2010associated genes. In the group of 100 children with (likely) pathogenic <jats:italic>COL1A1\/A2<\/jats:italic> variants, the proportions of phenotypes 1, 3, and 4 were 24%, 44%, and 32%, respectively. Consanguinity was 10%, which was less when compared to the other OI\u2010associated genes. The age of the first fracture was primarily at birth or before 6 months, particularly in severe types of OI such as Type III. Blue sclerae were observed in 84 patients, most commonly associated with OI Type I. Dentinogenesis imperfecta (DI) was present in 47 patients, typically seen in Types III and IV. Radiological features included Wormian bones in 58 patients, vertebral fractures in 46, and spine deformities in 16. Lower limb deformities were present in 90% of cases, with a higher prevalence in more severe forms of OI, while upper limb deformities were noted in 39%. Among the 22 patients receiving regular pamidronate therapy, there was a noticeable improvement in bone density, emphasizing the therapy's effectiveness, particularly in managing moderate to severe OI types. Genotypically, we report (likely) pathogenic 56 <jats:italic>COL1A1<\/jats:italic> and 46 <jats:italic>COL1A2<\/jats:italic> variants, including 21 novel variants. Of the 66 missense variants, 29 were in <jats:italic>COL1A1<\/jats:italic> and 37 in <jats:italic>COL1A2<\/jats:italic> genes. Of these, 60 were glycine substitutions (28 in <jats:italic>COL1A1<\/jats:italic> and 32 in <jats:italic>COL1A2<\/jats:italic>) in the triple helix, the commonest being glycine to serine, associated with OI Type 3 in 28 individuals. The report highlights that 47.6% (100 out of 210 patients) of <jats:italic>COL1A1<\/jats:italic> and <jats:italic>COL1A2<\/jats:italic> gene variants were found in our cohort who underwent genetic analysis. This percentage is notably lower compared to other populations, where the percentage of identified <jats:italic>COL1A1\/2<\/jats:italic> variants has been reported to be higher.<\/jats:p>","DOI":"10.1002\/ajmg.a.64023","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:45:27Z","timestamp":1741754727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp><i>COL1A1<\/i><\/scp> and <scp><i>COL1A2<\/i><\/scp> Gene Variants Causing Osteogenesis Imperfecta in a Major Referral Center of India"],"prefix":"10.1002","volume":"197","author":[{"given":"Agnes","family":"Selina","sequence":"first","affiliation":[{"name":"Department of Paediatric Orthopaedics Christian Medical College  Vellore Tamil Nadu India"},{"name":"Centre for Stem Cell Research Christian Medical College  Vellore Tamil Nadu India"},{"name":"Manipal Academy of Higher Education  Manipal Karnataka 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