A novel mild variant of osteogenesis imperfecta type I
caused by a Gly1088Glu mutation in COL1A1
- Authors:
- Xin‑Yi Xia
- Wei‑Wei Li
- Na Li
- Qiu‑Yue Wu
- Ying‑Xia Cui
- Xiao‑Jun Li
View Affiliations
Affiliations: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P.R. China
- Published online on: March 28, 2014 https://doi.org/10.3892/mmr.2014.2084
-
Pages:
2187-2190
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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.
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