Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China.
Nat Genet. 2012 Oct;44(10):1156-60. doi: 10.1038/ng.2409. Epub 2012 Sep 16.
Disseminated superficial actinic porokeratosis (DSAP) is an autosomal dominantly inherited epidermal keratinization disorder whose etiology remains unclear. We performed exome sequencing in one unaffected and two affected individuals from a DSAP family. The mevalonate kinase gene (MVK) emerged as the only candidate gene located in previously defined linkage regions after filtering against existing SNP databases, eight HapMap exomes and 1000 Genomes Project data and taking into consideration the functional implications of the mutations. Sanger sequencing in 57 individuals with familial DSAP and 25 individuals with sporadic DSAP identified MVK mutations in 33% and 16% of these individuals (cases), respectively. All 14 MVK mutations identified in our study were absent in 676 individuals without DSAP. Our functional studies in cultured primary keratinocytes suggest that MVK has a role in regulating calcium-induced keratinocyte differentiation and could protect keratinocytes from apoptosis induced by type A ultraviolet radiation. Our results should help advance the understanding of DSAP pathogenesis.
播散性浅表性光线性角化病（DSAP）是一种常染色体显性遗传的表皮角化障碍，其病因仍不清楚。我们对一个 DSAP 家族的一个未受影响者和两个受影响者进行了外显子组测序。在过滤现有 SNP 数据库、八个 HapMap 外显子组和 1000 基因组计划数据并考虑突变的功能影响后，甲羟戊酸激酶基因（MVK）作为唯一位于先前定义的连锁区域的候选基因出现。在 57 名有家族性 DSAP 的个体和 25 名散发性 DSAP 的个体中进行 Sanger 测序，分别在 33%和 16%的这些个体（病例）中发现了 MVK 突变。在我们的研究中发现的 14 个 MVK 突变在 676 名没有 DSAP 的个体中均不存在。我们在培养的原代角质形成细胞中的功能研究表明，MVK 在调节钙诱导的角质形成细胞分化中起作用，并能保护角质形成细胞免受 A 型紫外线诱导的凋亡。我们的研究结果应该有助于深入了解 DSAP 的发病机制。
