Mutations in connexin31 underlie recessive as well as dominant non-syndromic hearing loss
Mutations in connexin31 underlie recessive as well as dominant non-syndromic hearing loss
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DOI：
10.1093/hmg/9.1.63
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发表时间：
2000-01-01
影响因子：
3.5
通讯作者：
Nance, WE
中科院分区：
文献类型：
--
作者：
Liu, XZ;Xia, XJ;Nance, WE
编码连接蛋白31 （Cx31）的GJB3基因突变可导致显性非综合征型听力损失（DFNA2），为了确定该位点的突变是否也可导致隐性非综合征型耳聋，我们筛选了25个中国隐性耳聋家族，并在两个家族中发现了Cx31突变的复合杂合子。这两个家庭中的三个受影响的人出生于非近亲父母，并且患有早发性双侧感音神经性听力损失。在两个家庭中，在受影响的个体和未受影响的个体中观察到不同的SSCP模式。两个家族的序列分析显示，一个等位基因帧内3 bp缺失（423-425delATT），导致密码子141处异亮氨酸残基缺失，另一个等位基因423A- >G翻转，导致密码子141处Ile- >Val替换（I141V），这两个突变在100个不相关对照受试者的DNA中均未检测到。改变的异亮氨酸残基位于第三个保守的a-螺旋跨膜结构域（M3）内，这对间隙连接孔壁的形成至关重要。异亮氨酸残基141的缺失和它在两个家族中被缬氨酸取代都会改变M3的结构，损害间隙连接的功能。目前的数据表明，与connexin26的突变一样，Cx31的突变可导致隐性和显性形式的非综合征性耳聋。
Mutations in the GJB3 gene encoding connexin31 (Cx31) can cause a dominant non-syndromic form of hearing loss (DFNA2), To determine whether mutations at this locus can also cause recessive non-syndromic deafness, we screened 25 Chinese families with recessive deafness and identified in two families affected individuals who were compound heterozygotes for Cx31 mutations. The three affected individuals in the two families were born to nonconsanguineous parents and had an early onset bilateral sensorineural hearing loss. In both families, differing SSCP patterns were observed in affected and unaffected individuals. Sequence analysis in both families demonstrated an in-frame 3 bp deletion (423-425delATT) in one allele, which leads to the loss of an isoleucine residue at codon 141, and a 423A-->G transversion in the other allele, which creates an Ile-->Val substitution at codon 141 (I141V), Neither of these two mutations was detected in DNA from 100 unrelated control subjects. The altered isoleucine residue lies within the third conserved a-helical transmembrane domain (M3), which is critical for the formation of the wall of the gap junction pore. Both the deletion of the isoleucine residue 141 and its substitution to valine in the two families could alter the structure of M3, and impair the function of the gap junction. The present data demonstrate that, like mutations in connexin26, mutations in Cx31 can lead to both recessive and dominant forms of nonsyndromic deafness.