Molecular diagnosis of a Chinese pedigree with osteogenesis imperfecta type I

Objective To perform molecular diagnosis for a Chinese pedigree with osteogenesis imperfecta type Ⅰ.Methods Thirty pairs of primers were designed tO amplify all the 52 exons,exon boundaries and promoter region of the COL1A1 gene from genomic DNA of peripheral blood cells of the family members.The PCR products were purified and directly sequenced.To check the mutation in normal controls.the genomic DNA from peripheral blood cells of the index patient,his mother and 60 normal controls were analyzed by amplification refractory mutation system.ResultsA missense mutation of GAT ＞CAT was identified at codon 1441 of the COL1A1 gene from the family,which resulted in the replacement of aspartic acid by histidine(D1441H).This mutation was not found in a group of 60 normal controls.Conclusion The method for molecular diagnosis of osteogenesis imperfecta was established and a novel COL1A1 gene mutation,D1441H,was identified in the Chinese pedigree with osteogenesis imperfecta type Ⅰ. Key words: osteogenesis imperfecta;  COL1A1 gene; gene mutation; molecular diagnosis