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

作者：Liu, Wei; Gu, Feng; Ji, Jian; Lu, Duanyang; Li, Xiaorong; Ma, Xu^*

来源：Molecular Vision, 2007, 13(38-39): 360-365.

• I CELL STRAINS
• NULL ALLELES
• COLLAGEN
• GENE
• SUBSTITUTION
• CHAIN
• HETEROGENEITY
• FEATURES
• PATIENT
• CORNEAL

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.

• 出版日期2007-3-9
• 单位中国医学科学院北京协和医院; 国家卫生计生委科学技术研究所; 天津医科大学