成骨不全症Ⅳ型家系COL1A1基因突变

COL1A1 gene mutation in a family with osteogenesis imperfecta type Ⅳ

目的报告1个常染色体显性遗传的成骨不全症Ⅳ型家系COL1A1基因突变,探讨基因型与表型的关系。方法提取该家系所有患者及正常成员和50个健康人对照血样本的DNA。对先证者COL1A1基因的启动子、51个外显子和外显子/内含子剪接处进行PCR并对产物测序。对家系的另外4个患者和有血缘关系的健康者及50名健康对照者的第25外显子测序。结果先证者和所有患者COL1A1基因测序均显示第25外显子的7872位置碱基发生杂合突变(g.7872G>A,c.1678G>A,p.G560S),但家系中健康者和无血缘关系的50名健康对照者均无此改变,与临床诊断一致。先证者该基因的其他位置未见突变。结论COL1A1基因G560S突变产生的表型是成骨不全症Ⅳ型。50岁以后有听力减退,这是先前相同突变没有描述过的表型。

Objective To report the mutation of COL1A1 gene in a Chinese family with osteogenesis imperfecta （OI） type Ⅳ, and to investigate the relationship between the genotype and phenotype. Methods Promotor,51 exons and exon/intron boundaries of COL1A1 gene from the proband were amplified and sequenced. The exon 25 was amplified and sequenced from the 4 other patients with OI, the healthy relatives of the family, and 50 controls respectively. Results Direct sequencing of COL1A1 gone revealed a mutation （ g. 7872 G 〉 A,c. 1678 G 〉 A,p. G560S） in the proband and the other patients. No mutation was found in the normal relatives and 50 controls. No other mutation was found in COL1A1 gene from the proband. Conclusions The mutation of COL1A1 gene is responsible for the familial OI type Ⅳ. The phenotype of bilateral progressive loss of hearing in the same mutation has not been reported before.