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目的分析中国常染色体显性遗传非综合征性耳聋(DFNA)群体凝血因子 C 同源物(COCH)基因突变发生率及突变谱。方法在我国汉族人群中收集26个 DFNA 家系、19个遗传方式不明的迟发性耳聋小家系、22例迟发性耳聋散发病例和100例正常对照者的临床资料及外周静脉血并提取 DNA,采取 PCR 扩增后直接测序的方法进行 COCH 全序列突变分析。结果在1个巨大DFNA 家系中发现 COCH 1625G>A 杂合突变,使原来542位的半胱氨酸突变成酪氨酸(C542Y);在1个遗传方式不明的迟发性耳聋小家系中发现 COCH 1535 T>C 杂合突变,使512位蛋氨酸突变为苏氨酸(M512T)。进化保守性分析提示 C542、M512在小鼠、牛、鸡和斑马鱼中高度保守。2个家系成员的表现型与基因型共分离。100例正常对照未见 COCH 突变。结论 COCH M512T 和 C542Y 突变是这2个迟发性耳聋家系患者致聋的分子病因。
Objective To analyze the incidence and mutation of clotting factor C (COCH) gene mutations in Chinese autosomal dominant non-syndromic hearing loss (DFNA) population. Methods A total of 26 DFNA pedigrees, 19 small deaf families with unknown inheritance, 22 cases of delayed deafness cases and 100 normal controls were collected from the Han nationality in our country and peripheral venous blood samples were collected for DNA extraction. The full-length COCH mutation analysis was performed by direct sequencing after PCR amplification. The results showed that COCH 1625G> A heterozygous mutation was found in one huge DFNA pedigree, and the original 542 cysteine was mutated to tyrosine (C542Y). In a small inherited deafness family with deafness COCH 1535 T> C heterozygous mutation was found to mutate the methionine at position 512 to threonine (M512T). Evolutionary conservation analysis suggests that C542 and M512 are highly conserved in mice, cattle, chickens and zebrafish. Two members of the phenotype and genotype co-segregation. 100 cases of normal control no COCH mutation. Conclusions COCH M512T and C542Y mutations are the molecular causes of deafness in these two families with delayed deafness.