Autosomal Dominant Prelingual Hearing Loss With Palmoplantar Keratoderma Syndrome: Variability in Clinical Expression From Mutations of R75W and R75Q in the GJB2 Gene
Autosomal Dominant Prelingual Hearing Loss With Palmoplantar Keratoderma Syndrome: Variability in Clinical Expression From Mutations of R75W and R75Q in the GJB2 Gene
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DOI：
10.1002/ajmg.a.33464
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发表时间：
2010-07-01
影响因子：
2
通讯作者：
Arndt, Susan
中科院分区：
文献类型：
--
作者：
Birkenhaeger, Ralf;Lueblinghoff, Nicola;Arndt, Susan
每1000名新生儿中就有1到3人在出生时患有严重的听力障碍，其中约一半的病例是由遗传原因造成的。听力障碍的遗传原因非常复杂。在所有由遗传引起的非综合征性听力损失病例中，约有一半可归因于GJB2基因（连接蛋白26）的突变和GJB6基因-（连接蛋白30）的缺失。到目前为止，已经鉴定出大约90种不同的GJB2基因突变，其中大多数是常染色体隐性基因。10个突变是常染色体显性的，在大多数情况下与各种皮肤病有关：角膜炎-鱼鳞病-耳聋（KID）综合征、Vohwinkel综合征和伴有耳聋的掌跖角化皮病。迄今为止，已确定下列突变可导致掌跖角化病综合征伴耳聋；Gly59Ala, Gly59Arg, His73Arg， Arg75Trp和Arg75Gln。我们正在报道四名患有严重听力障碍的患者。他们是三个不相关家族的成员，他们是Arg75Trp或Arg75Gln突变的携带者，但与其他出版物的患者不同，并非所有患者都表现为掌跖角化病综合征。我们的研究为GJB2基因突变与伴有掌跖角化病的综合征性听力障碍之间的相关性提供了额外的证据。(C) 2010 Wiley-Liss, Inc。
About one to three of a 1,000 neonates are afflicted at birth with a serious hearing impairment, with about half of the cases due to genetic causes. Genetic causes of hearing impairment are very heterogeneous. About half of all cases of genetically caused nonsyndromic hearing loss can be ascribed to mutations in the GJB2 gene (connexin 26) and to deletions in the GJB6 gene-(connexin 30). Thus far, about 90 different mutations have been identified in the GJB2 gene, of which the majority are autosomal recessive. Ten mutations are autosomal dominant and are in most cases associated with various skin diseases: the keratitis-ichthyosis-deafness (KID) syndrome, Vohwinkel syndrome and palmoplantar keratoderma with deafness. To date, the following mutations have been identified which lead to the Palmoplantar Keratoderma syndrome with deafness; Gly59Ala, Gly59Arg, His73Arg, Arg75Trp, and Arg75Gln. We are reporting on four patients with severe hearing impairment. They are members of three unrelated families, who are carriers of mutations Arg75Trp or Arg75Gln, but unlike patients of other publications, do not all present with Palmoplantar Keratoderma syndrome. Our investigations document additional evidence for the correlation between the cited mutations in the GJB2 gene and a syndromic hearing impairment with palmoplantar keratoderma. (C) 2010 Wiley-Liss, Inc.