Epidermolysis bullosa simplex in Israel - Clinical and genetic features
Epidermolysis bullosa simplex in Israel - Clinical and genetic features
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DOI：
10.1001/archderm.139.4.498
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发表时间：
2003-04-01
影响因子：
--
通讯作者：
Sprecher, E
中科院分区：
文献类型：
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作者：
Ciubotaru, D;Bergman, R;Sprecher, E
背景：单纯大疱性表皮病（EBS）是大疱性表皮病中最常见的一种。该疾病的特征是表皮内水疱，在大多数情况下，由于细胞角蛋白基因5（K5）或14（K14）的突变。在美国和欧洲的广泛研究表明，EBS几乎总是在一个常染色体显性fashion.Objective：要评估的可能性，EBS的分子特征可能会有所不同，根据类型的人口studied.Design：我们评估了10个以色列家庭诊断为有EBS和比较他们的临床和遗传特征与以前的观察。受影响的个体接受了完整的临床评价。使用聚合酶链反应扩增、直接测序和随后的突变验证来评估来自所有家庭成员的DNA中的K5或K14突变。此外，特定的情况下，基因分型使用面板的微卫星标记跨越K14 locus.Results：8个不同的致病突变K5（3个突变）和K14（5个突变）被确定。其中六种突变是新的。突变包括2个无义突变和6个错义突变。三分之一的受影响家庭以隐性方式遗传EBS，这与欧洲和美国以前的观察结果相反。此外，我们发现了一个独特的情况下，导致复合杂合性错义和无义突变K14。纯合子无义突变与严重的phenotype.Conclusion：本研究表明，一个独特的突变谱和一个显着不同的模式，在一系列以色列家庭的EBS的遗传与欧洲或美国提取的家庭相比。
Background: Epidermolysis bullosa simplex (EBS) is the most common form of epidermolysis bullosa. The disease is characterized by intraepidermal blistering due in most cases to mutations in cytokeratin genes 5 (K5) or 14 (K14). Extensive studies in the United States and Europe have shown that EBS is almost always inherited in an autosomal dominant fashion.Objective: To assess the possibility that the molecular features of EBS may differ according to the type of population studied.Design: We assessed 10 Israeli families diagnosed as having EBS and compared their clinical and genetic features with previous observations. Affected individuals underwent complete clinical evaluation. DNA from all family members was assessed for mutations in K5 or K14 using polymerase chain reaction amplification, direct sequencing, and subsequent mutation verification. In addition, specific cases were genotyped using a panel of microsatellite markers spanning the K14 locus.Results: Eight distinct pathogenic mutations in K5 (3 mutations) and K14 (5 mutations) were identified. Six of these mutations are novel. The mutations included 2 nonsense mutations and 6 missense mutations. A third of the affected families inherited EBS in a recessive fashion, in contrast with previous observations in Europe and the United States. In addition, we identified a unique case that resulted from compound heterozygosity for a missense and a nonsense mutation in K14. Homozygous nonsense mutations were strongly associated with a severe phenotype.Conclusion: The present study demonstrates a unique mutation spectrum and a strikingly different pattern of inheritance for EBS in a series of Israeli families compared with families of European or US extraction.