title: Mutation spectrum of COL1A1 and COL1A2 genes in Indian patients with osteogenesis imperfecta.
abstract: Osteogenesis imperfecta (OI) is a condition of decreased bone density with heterogeneous etiologies. Most of the cases are inherited in an autosomal dominant fashion and are caused by mutations in the COL1A1 or COL1A2 genes. Since these two genes are very large, there are no data about mutations in Indian patients with OI. We selected 35 Indian patients who were clinically diagnosed with OI and all exons of both the genes were sequenced. Mutations in COL1A1 (14 cases, 6 novel) and COL1A2 (11 cases, 7 novel) were identified in 25 patients. A total of 55 polymorphisms were identified in both the genes with eight novel variants in the coding region, and nine novel variants in the non-coding regions. No mutation was detected in 10 patients. Six of them were from consanguineous families, with one or two similarly affected siblings suggesting possible autosomal recessive inheritance. If we exclude families with consanguinity, mutations were identified in 25 out of 29 families giving 86% mutation detection rate. Mutations in COL1A1 accounted for 56% of the cases and COL1A2 44%, which is similar to the reported rate worldwide.
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Joshi
authors.initials: J
authors.lastname: Stephen
authors.forename: Anju
authors.initials: A
authors.lastname: Shukla
authors.forename: Ashwin
authors.initials: A
authors.lastname: Dalal
authors.forename: Katta Mohan
authors.initials: KM
authors.lastname: Girisha
authors.forename: Hitesh
authors.initials: H
authors.lastname: Shah
authors.forename: Neerja
authors.initials: N
authors.lastname: Gupta
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kabra
authors.forename: Preeti
authors.initials: P
authors.lastname: Dabadghao
authors.forename: Kosei
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Shubha R
authors.initials: SR
authors.lastname: Phadke
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D050723:Fractures, Bone / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain
keywords: COL1A1; COL1A2; India; mutation; osteogenesis imperfecta