Identification of a novel COL1A1 frameshift mutation, c.700delG,in a Chinese osteogenesis imperfecta family

Osteogenesis imperfecta (OI) is a family of genetic disorders associated with boneloss and fragility. Mutations associated with OI have been found in genes encodingthe type I collagen chains. People with OI type I often produce insufficient α1-chaintype I collagen because of frameshift, nonsense, or splice site mutations inCOL1A1 or COL1A2. This report is of a Chinesedaughter and mother who had both experienced two bone fractures. Because skeletalfragility is predominantly inherited, we focused on identifying mutations inCOL1A1 and COL1A2 genes. A novel mutation inCOL1A1, c.700delG, was detected by genomic DNA sequencing in themother and daughter, but not in their relatives. The identification of this mutationled to the conclusion that they were affected by mild OI type I. Open reading frameanalysis indicated that this frameshift mutation would truncate α1-chain type Icollagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain1,464 residues. The clinical data were consistent with the patients’ diagnosis ofmild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combinedwith previous reports, identification of the novel mutationCOL1A1-c.700delG in these patients suggests thatadditional genetic and environmental factors may influence the severity of OI.