A novel COL1A1 nonsense mutation causing osteogenesisimperfecta in a Chinese family

[摘要] Purpose: To identify the genetic defect of osteogenesis imperfecta(OI) type I in a large Chinese family of five generations.Methods: Seventeen members in an OI type I family were recruited,and clinical examinations were performed. All members were genotypedwith microsatellite markers at loci associated with OI. A two-point LODscore was calculated using the Linkage package. A mutation was detectedby direct sequencing.Results: All affected individuals in the family had fractured a bonemore than once, and their sclerae were blue. Significant evidence oflinkage was obtained at markers D17S1180 (LOD score [Z]=2.91, atrecombination fraction [θ]=0.0) and D17S1319 (Z=2.20, atθ=0.0), respectively. Sequencing of the COL1A1 gene revealed aC>T transition in exon 36, which caused a substitution of Gln atcodon 644 to a stop codon (Q644X). This mutation was not observed inunaffected or 100 normal unrelated individuals.Conclusions: This study is the first report that OI is associatedwith the mutation Q644X of COL1A1.

[学科分类] 生物化学/生物物理