非综合征性耳聋患者连接蛋白26基因突变的研究

Mutations in the connexin 26 gene in patients with nonsyndromic hearing impairment

目的 探讨中国人非综合征性耳聋患者连接蛋白 2 6 (connexin 2 6 ,Cx2 6 )基因突变频率和特性。方法 收集中国散发先天性聋哑儿童 16例 ,常染色体隐性遗传性聋 39例 (39个家系 ) ,10岁前开始听力下降的常染色体显性遗传性聋 30例 (30个家系 )和健康对照组 10 0例。聚合酶链反应 单链构象多态 (singlestrandconformationalpolymorphismanalysisofpolymerasechainreaction ,PCR SSCP)分析初筛可疑突变者 ,SSCP分析发现异常构象带后再行DNA测序。结果 健康对照组中 15例发现 5种多态性改变 ,耳聋患者中 10例发现 6种多态性改变。散发先天性聋哑和常染色体隐性遗传非综合征性耳聋中未发现致病突变。 1个常染色体显性遗传性聋家系发现所有患者 (3例 )Cx2 6基因的编码区2 99 30 0位碱基AT杂合性缺失 ,导致移码突变 ,翻译的蛋白质截短 ,该家系听力正常者无此突变。结论 蒙古人种中常染色体隐性遗传性非综合征性耳聋的Cx2 6基因突变率可能低于其他人种。Cx2 6基因编码区 2 99 30

Objective To determine the prevalence and characteristics of deafness causing mutations in Connexin 26(Cx26,GJB2) gene in Chinese with nonsyndromic hearing impairment(NSHI). Methods Study subjects are all Chinese including 16 infants with sporadic congenital deaf mutism, 39 patients with autosomal recessive hereditary hearing loss, 30 patients with autosomal dominant hereditary hearing loss and 100 normal adults. The subjects were screened for base variations by single strand conformational polymorphism (SSCP) analysis of the amplified products of polymerase chain reaction (PCR). Those who were found have abnormal conformational band were sequenced. Results Five kinds of polymorphism were found in 15 cases of controls and six kinds of polymorphism in 10 patients. No mutation was found in Cx26 gene in Chinese with autosomal recessive NSHI. Heterozygous deletion AT at position 299 300 of Cx26 cDNA, which results in premature chain termination, was found in a pedigree with autosomal dominant hereditary nonsyndromic hearing loss. Conclusion The prevalence of deafness causing mutations in Cx26 gene in Chinese with autosomal recessive NSHI maybe is lower than that of other ethnic groups. Heterozygous deletion AT at position 299 300 of Cx26 cDNA can lead to autosomal dominant hereditary hearing loss (DFNA3).