A novel COL1A1 nonsense mutation causing osteogenesis imperfecta in a Chinese family.

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 genotyped with microsatellite markers at loci associated with OI. A two-point LOD score was calculated using the Linkage package. A mutation was detected by direct sequencing.

RESULTS

All affected individuals in the family had fractured a bone more than once, and their sclerae were blue. Significant evidence of linkage was obtained at markers D17S1180 (LOD score [Z]=2.91, at recombination fraction [theta]=0.0) and D17S1319 (Z=2.20, at theta=0.0), respectively. Sequencing of the COL1A1 gene revealed a C>T transition in exon 36, which caused a substitution of Gln at codon 644 to a stop codon (Q644X). This mutation was not observed in unaffected or 100 normal unrelated individuals.

CONCLUSIONS

This study is the first report that OI is associated with the mutation Q644X of COL1A1.