角皮病致病基因GJB4在遗传性耳聋中的研究

目的连接蛋白基因和遗传性耳聋及角皮病有明确的相关性.现有4个连接蛋白基因突变可导致角皮病,即:GJB4、GJB2、GJB3和GJB6,其中3个基因既可导致遗传性耳聋,即GJB2、GJB3和GJB6,而GJB4是否与遗传性耳聋相关还有待于进一步证实.为证实GJB4和遗传性耳聋的相关性,在非综合征型遗传性耳聋中进行突变检测.方法本实验采用PCR-直接测序法对60个非综合征型遗传性耳聋家系先证者进行GJB4的突变检测,其中32个显性遗传,28个隐性遗传.结果发现了四种碱基改变:109G＞A、3'UTR 17 A＞G、611A＞C和507C＞G.109G＞A和3'UTR 17A＞G是新发现的碱基改变,但在家系突变检测中证实为多态.611A＞C和507C＞G两种碱基改变是已报道的多态,611A＞C是我们检测到的最常见的多态.结论本研究发现了GJB4的109G＞A和3'UTR 17 A＞G两种新多态,为今后进一步研究打下了基础,但未能最终证实GJB4为遗传性耳聋的致病基因,可是从该基因背景来分析GJB4仍可能是一个很好的耳聋候选基因,有待于扩大家系收集范围进一步检测.

Keratoderma-related gene GJB4 may involved in hereditary hearing loss

Objective Connexins have been associated with hereditary hearing loss and keratoderma. Four genes cause keratoderma(GJB4, GJB3, GJB2 and GJB6). Three of them are involved in deafness(GJB3, GJB2 and GJB6). It is unknown whether, as for other keratoderma-associated connexins(GJB3, GJB2 and GJB6), GJB4 mutations also result in non-syndromic deafness. It is necessary to prove the correlation between GJB4 and hereditary hearing loss. Mothed We have performed mutational analysis of the GJB4 coding region in 60 Chinese subjects with non-syndromic deafness(32 with dominant inheritance, 28 with recessive inheritance) by PCR-direct sequencing. Result Four sequence changes were found:109G>A? 3'UTR+17 A >G? 611A>C and 507C>G. 109G>A and 3'UTR+17 A >G were new polymorphisms. 611A>C and 507C>G mutations were previously reported polymorphisms. 611A>C was the most common polymorphism detected. Conclusion We detected two new polymorphisms in GJB4. GJB4 did not yet prove to be the disease gene for hereditary hearing loss, but GJB4 is still a strong candidate. Further studies of mutational analysis of GJB4 gene will be needed to carry out in more pedigrees.