Nature Genet：科学家发现皮肤疾病致病基因的突变

由安徽医科大学和BGI领导的一中国研究小组最新证实甲羟戊酸激酶基因（MVK）遗传突变和弥漫性浅表性光化性汗孔角化症（DSAP）之间有密切联系。这项研究发现为揭示DSAP遗传发病机制迈进了一大步，有助于开发分子诊断和治疗技术。研究结果发表在<em>Nature Genetics</em>杂志上。<!--more-->

DSAP是一种罕见的非肿瘤类型、非传染性的皮肤疾病，会导致患者胳膊和腿皮肤干燥，发痒病变。持续日晒是导致患DSAP的一个危险因素。虽然DSAP是一种慢性疾病，它是可以治疗的，但一直以来这种疾病不能得到完全治愈。

在这项研究中，研究人员对属于同一个有DSAP疾病史家庭的两例受影响和一例未受影响的个体进行基因组测序。通过变体分析和数据过滤，研究人员猜测MVK基因是唯一一个与DSAP发病相关的候选基因。

MVK编码蛋白质甲羟戊酸激酶，甲羟戊酸激酶是一个重要的甲羟戊酸途径的酶，通过提供必需的生物活性分子多种细胞过程。MVK的表达对角质形成细胞生物活性的影响，研究人员表示，MVK能调节钙诱导的角质形成细胞的分化，同时MVK的表达可以防止因UVA引起的角质形成细胞的凋亡。

该项目的高级科学家Tao Jiang说，我们的研究DSAP的发病机制提供了新的见解，并确定MVK突变是基因诊断和临床治疗该类疾病的最佳的候选靶标。

这项研究的通讯作者安徽医科大学Xuejun Zhang说，基因组测序是一种有效的方法来鉴定单基因遗传性疾病的疾病基因，这项研究不仅标志着中国在世界上寻找单基因遗传病的致病基因处于最先进的水平，用死也为揭示DSAP的发病机制、进行疾病风险预测、药物开发、临床诊断和治疗提供了科学依据。

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<img src="http://www.bioon.com/biology/UploadFiles/201209/2012091710414069.gif" alt="" width="115" height="150" border="0" />

<a title="" href="http://dx.doi.org/10.1038/ng.2409" target="_blank">doi:10.1038/ng.2409</a>
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<br/><strong>Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis.</strong><br/>


Sheng-Quan Zhang, Tao Jiang, Min Li, Xin Zhang, Yun-Qing Ren, Sheng-Cai Wei, Liang-Dan Sun, Hui Cheng, Yang Li, Xian-Yong Yin, Zheng-Mao Hu, Zhen-Ying Wang, Yuan Liu, Bi-Rong Guo, Hua-Yang Tang, Xian-Fa Tang, Yan-Tao Ding, Jian-Bo Wang, Ping Li, Bao-Yu Wu, Wen Wang, Xiang-Feng Yuan, Jun-Sheng Hou, Wei-Wei Ha, Wen-Ju Wang, Yu-Juan Zhai, Jing Wang, Fang-Fang Qian, Fu-Sheng Zhou, Gang Chen, Xian-Bo Zuo, Xiao-Dong Zheng, Yu-Jun Sheng, Jin-Ping Gao, Bo Liang, Pan Li, Jun Zhu, Feng-Li Xiao, Pei-Guang Wang, Yong Cui, Hui Li, Sheng-Xiu Liu, Min Gao, Xing Fan, Song-Ke Shen, Ming Zeng, Guang-Qing Sun, Yu Xu, Jing-Chu Hu, Ting-Ting He, Ying-Rui Li, Huan-Ming Yang, Jian Wang, Zhong-Yi Yu, Hui-Feng Zhang, Xin Hu, Ke Yang, Jie Wang, Shi-Xiang Zhao, You-Wen Zhou, Jian-Jun Liu, Wei-Dong Du, Li Zhang, Kun Xia, Sen Yang, Jun Wang, Xue-Jun Zhang.

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.

<br/>来源：生物谷

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