五个患有条纹状掌跖角化病的巴基斯坦家庭中桥粒芯糖蛋白1基因的突变
Mutations in the desmoglein 1 gene in five Pakistani families with striate palmoplantar keratoderma.
作者信息
Dua-Awereh Martha B, Shimomura Yutaka, Kraemer Liv, Wajid Muhammad, Christiano Angela M
机构信息
Department of Dermatology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street VC-1526, New York, NY 10032, United States.
出版信息
J Dermatol Sci. 2009 Mar;53(3):192-7. doi: 10.1016/j.jdermsci.2008.11.005. Epub 2009 Jan 20.
BACKGROUND
Striate palmoplantar keratoderma (SPPK; OMIM #148700) is a rare autosomal dominant genodermatosis characterized by linear hyperkeratosis on the digits and hyperkeratosis on the palms and soles. SPPK is known to be caused by heterozygous mutations in either the desmoglein 1 (DSG1), desmoplakin (DSP), or keratin 1 (KRT1) genes.
OBJECTIVE
To define the molecular basis of SPPK in five Pakistani families showing a clear autosomal dominant inheritance pattern of SPPK.
METHODS
Based on previous reports of DSG1 mutations in SPPK, we performed direct sequencing of the DSG1 gene of all five families.
RESULTS
Mutation analysis resulted in the identification of one recurrent mutation (p.R26X) and four novel mutations (c.Ivs4-2A>G, c.515C>T, c.Ivs9-3C>G, and c.1399delA) in the DSG1 gene. Each mutation is predicted to cause haploinsufficiency of DSG1 protein.
CONCLUSION
The results of our study further underscore the significance of the desmoglein gene family in diseases of epidermal integrity.
背景
线状掌跖角化病（SPPK；OMIM #148700）是一种罕见的常染色体显性遗传性皮肤病，其特征为手指上的线状角化过度以及手掌和脚底的角化过度。已知SPPK是由桥粒芯糖蛋白1（DSG1）、桥粒斑蛋白（DSP）或角蛋白1（KRT1）基因的杂合突变引起的。
目的
确定五个呈现明显常染色体显性遗传模式的巴基斯坦家族中SPPK的分子基础。
方法
基于先前关于SPPK中DSG1突变的报道，我们对所有五个家族的DSG1基因进行了直接测序。
结果
突变分析在DSG1基因中鉴定出一个复发性突变（p.R26X）和四个新突变（c.Ivs4 - 2A>G、c.515C>T、c.Ivs9 - 3C>G和c.1399delA）。每个突变预计会导致DSG1蛋白单倍体不足。
结论
我们的研究结果进一步强调了桥粒芯糖蛋白基因家族在表皮完整性疾病中的重要性。
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