A novel missense mutation in GJB2 disturbs gap junction protein transport and causes focal palmoplantar keratoderma with deafness
A novel missense mutation in GJB2 disturbs gap junction protein transport and causes focal palmoplantar keratoderma with deafness
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DOI：
10.1136/jmg.2007.052332
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发表时间：
2008-03-01
影响因子：
4
通讯作者：
van Steensel, M. A. M.
中科院分区：
文献类型：
--
作者：
de Zwart-Storm, E. A.;Hamm, H.;van Steensel, M. A. M.
缝隙连接是介导细胞间快速通讯的细胞间通道。它们由连接蛋白组成，连接蛋白是一种小的跨膜蛋白，属于整个动物王国中发现的一个大家族。在皮肤中，几种连接蛋白表达并参与表皮生长和分化的调节。皮肤表达的间隙连接基因之一是GJB 2，其编码连接蛋白26，并与多种角质化疾病相关。在这里，我们报告了一个家庭与一个新的GJB 2突变（p.His73Arg）引起的综合征局灶性掌跖角化病与严重的进行性感音神经性听力障碍，一个表型让人想起Vohwinkel综合征。使用荧光连接蛋白融合蛋白，我们表明，突变诱导的运输缺陷类似于Vohwinkel综合征突变p.Asp66His。共转染到表达野生型连接蛋白26的细胞中显示突变体对连接蛋白运输具有显性负效应。我们认为GJB 2突变可能存在较弱的基因型-表型相关性。
Gap junctions are intercellular channels that mediate rapid intercellular communication. They consist of connexins, small transmembrane proteins that belong to a large family found throughout the animal kingdom. In the skin, several connexins are expressed and are involved in the regulation of epidermal growth and differentiation. One of the skin expressed gap junction genes is GJB2, which codes for connexin 26 and is associated with a wide variety of keratinisation disorders. Here, we report on a family with a novel GJB2 mutation (p.His73Arg) causing a syndrome of focal palmoplantar keratoderma with severe progressive sensorineural hearing impairment, a phenotype reminiscent of Vohwinkel syndrome. Using fluorescent connexin fusion proteins, we show that the mutation induces a transport defect similar to that found for the Vohwinkel syndrome mutation p.Asp66His. Co-transfection into cells expressing wild type connexin26 shows that the mutant has a dominant negative effect on connexin trafficking. We suggest that there may be a weak genotype-phenotype correlation for mutations in GJB2.