Mutation detection of COL1A1 gene in a pedigree with osteogenesis imperfecta]

Osteogenesis imperfecta (OI) is heritable bone fragility,which is inherited as an autosomal dominant trait clinical presentation. Clinical symptom, in general, is dominantly inherited OI with blue sclerae, hearing loss and mild-moderate skeletal deformity. Genetic loci of OI have been mapped to17q21.31-q22 and 7q22.1, in which COL1A1 and COL1A2 are known to be the causal genes. In this work,we performed linkage analysis in a kindred with autosomal dominant hereditary OI. A tight linkage to the markers on chromosome 17q21.31-q22 (maximum two-point lod score: 9.31 at theta = .00) was observed. Sequence analysis of COL1A1 revealed a single-base mutation that converted the consensus sequence at the 5' end of intron 26 from GT to AT to form an abnormal splicing site leading to OI.