Mutation Update for the CSB/ERCC6 and CSA/ERCC8 Genes Involved in Cockayne Syndrome
Mutation Update for the CSB/ERCC6 and CSA/ERCC8 Genes Involved in Cockayne Syndrome
复制标题
DOI：
10.1002/humu.21154
复制
发表时间：
2010-02-01
期刊：
影响因子：
3.9
通讯作者：
Dollfus, H.
中科院分区：
文献类型：
--
作者：
Laugel, V.;Dalloz, C.;Dollfus, H.
Cockayne综合征是一种常染色体隐性遗传性多系统疾病，以神经和感觉障碍、恶病质侏儒症和光敏为主要特征。这种罕见的疾病与CSB/ERCC6和CSA/ERCC8基因突变有关，这些基因编码的蛋白参与了转录，耦合的DNA修复途径。Cockayne综合征的临床范围广泛，从严重的产前表现到轻度和晚发性症状。我们回顾了到目前为止已发表的45个CsA和CSB突变，我们报告了43个这些基因的新突变以及相应的临床数据。在报告的84个家系中，52个(62%)有CSB基因突变。许多类型的突变散布在两个基因的整个编码序列上，但错义突变的簇可以被识别并突出特定基序在蛋白质中的作用。根据这些新的分子和临床数据，考虑了基因-表型相关性假说。报告了其他分子产前诊断的病例，并讨论了产前检测的策略。已经建立了两个基于网络的特定基因座数据库，以列出所有已确定的变异，并允许纳入未来的报告(www.umd.be/csa/和www.umd.be/csb/)。《哼唱变种人》31：113-126,2010。(C)2009年Wiley-Liss，Inc.
Cockayne syndrome is an autosomal recessive multisystem disorder characterized principally by neurological and sensory impairment, cachectic dwarfism, and photosensitivity. This rare disease is linked to mutations in the CSB/ERCC6 and CSA/ERCC8 genes encoding proteins involved in the transcription, coupled DNA repair pathway. The clinical spectrum of Cockayne syndrome encompasses a wide range of severity from severe prenatal forms to mild and late-onset presentations. We have reviewed the 45 published mutations in CSA and CSB to date and we report 43 new mutations in these genes together with the corresponding clinical data. Among the 84 reported kindreds, 52 (62%) have mutations in the CSB gene. Many types of mutations are scattered along the whole coding sequence of both genes, but clusters of missense mutations can be recognized and highlight the role of particular motifs in the proteins. Genotype-phenotype correlation hypotheses are considered with regard to these new molecular and clinical data. Additional cases of molecular prenatal diagnosis are reported and the strategy for prenatal testing is discussed. Two web,based locus-specific databases have been created to list all identified variants and to allow the inclusion of future reports (www.umd.be/CSA/ and www.umd.be/CSB/). Hum Mutant 31:113-126, 2010. (C) 2009 Wiley-Liss, Inc.