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目的在一组中国北方耳聋人群中进行 GJB2基因突变分子流行病学研究。方法调查214例散发聋病患者,分布在中国长江以北的14个省份,全部为汉族;另外募集正常听力者86名作为对照针对GJB2的编码区进行 PCR 扩增,然后直接测序检测突变,对测序结果进行分析。结果检测到 GJB2基因9种序列改变方式,其中良性多态有2种(79G→A、341A→G),致病突变6种(35delG、109G→A、235delC、504insGCAA、299-300delAT 和176-191dell6),另有一种序列改变方式(455A→C)。耳聋患者中携带纯合致病变10例,其中109G→A纯合突变3例,235delC 纯合突变7例;有21例患者携带 GJB2基因杂合致病突变,其中235delC 杂合突变9例,109G→A杂合突变6例,176-191dell6杂合突变3例,504insGCAA 杂合突变1例,35delG 杂合突变1例.299-300delAT 杂合突变1例。21例患者中复合杂合突变(235delC/176-191dell6、235delC/504insGCAA、455A→G/109G→A)3例。结论在中国耳聋人群中235delC 突变率最高,在语前聋患者中更是这样;而 GJB2基因的35delG 在中国耳聋人群中并不常见。GJB2基因突变在听神经病患者中的作用还有待进一步研究,GJB2基因突变可能不是导致大前庭水管综合征耳聋病理基础。
Objective To study the molecular epidemiology of GJB2 gene mutation in a group of deaf people in northern China. Methods A total of 214 cases of deafness were investigated in 14 provinces north of the Yangtze River in China. All of them were Han nationality. In addition, 86 normal hearing persons were recruited as controls to amplify the coding region of GJB2. Then, the mutations were detected by direct sequencing. Sequencing results were analyzed. Results Nine sequences of GJB2 gene were detected. There were two types of GJB2 gene (79G → A, 341A → G), six pathogenic mutations (35delG, 109G → A, 235delC, 504insGCAA, 299-300delAT and 176- 191dell6), another way to change the sequence (455A → C). Deafness in patients with homozygous lesions in 10 cases, of which 109G → A homozygous mutation in 3 cases, 235delC homozygous mutation in 7 cases; 21 patients carrying GJB2 gene heterozygous disease mutations, including 235delC heterozygous mutation in 9 cases, 109G → A heterozygous mutation in 6 cases, 176-191dell6 heterozygous mutation in 3 cases, 504insGCAA heterozygous mutation in 1 case, 35delG heterozygous mutation in 1 case.299-300delAT heterozygous mutation in 1 case. Among the 21 patients, there were 3 patients with complex heterozygous mutation (235delC / 176-191dell6, 235delC / 504insGCAA, 455A → G / 109G → A). Conclusions The highest rate of 235delC mutation is found in deafness population in China, especially in prelingual deafness patients. However, 35delG of GJB2 gene is not common in Chinese deafness population. The role of GJB2 mutations in patients with auditory neuropathy remains to be further studied, and mutations in the GJB2 gene may not be the underlying basis for deafness of the aquaporin syndrome.