title: A novel mild variant of osteogenesis imperfecta type I caused by a Gly1088Glu mutation in COL1A1.
abstract: Osteogenesis imperfecta (OI), also known as brittle bone disease, characterized by multiplicative osteopsathyrosis, blue sclera, dentinogenesis imperfecta and mild audition, is a rare inherited connective tissue disease. There are seven types of OI, I to VII, among which type I-IV are relatively common and associated with type I collagen. Defects in type I collagen synthesis or structure are responsible for the majority of clinical OI cases since collagen is the major matrix protein of all connective tissues. Type I collagen consists of two pro-α1 chains and one pro-α2 chain, which are encoded by two genes, COL1A1 and COL1A2, respectively. The two subunits have a Gly-X-Y repeat domain, of which glycine is highly conserved in the majority of species. Point mutations on these sites appear to trigger OI. In the current study, a heterozygous mutation, c.3263G>A, p.Gly1088Glu, was identified in the Gly-X-Y domain of type I collagen in an affected individual with type I OI. A lethal phenotype with the p.Gly1088Ala mutation was observed at the same site as the current findings. This suggests that variant characteristics of the substitution for Gly may trigger a varying degree of OI from lethal to mild, even when the mutation occurs at the same site. It is hypothesized that the study may provide insight into the phenotype-genotype association and may assist, not only in the clinical diagnosis, but also in investigating the mechanism of collagen-associated diseases.
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P.R. China.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Xia
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P.R. China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Li
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P.R. China.
authors.forename: Qiu-Yue
authors.initials: QY
authors.lastname: Wu
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P.R. China.
authors.forename: Ying-Xia
authors.initials: YX
authors.lastname: Cui
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P.R. China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D024042:Collagen Type I / Q000737:chemistry / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D011859:Radiography; D016415:Sequence Alignment
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain