来自安徽医科大学的Xue-Jun Zhang、深圳华大基因的Jun Wang及其同事在播散性浅表性光化性汗孔角化症(DSAP)中鉴定到甲羟戊酸激酶基因(MVK)发生了突变。MVK基因编码了甲羟戊酸激酶,该激酶参与了胆固醇和类异戊二烯的生物合成。这项研究为深入研究DSAP的具体发病机制奠定了重要基础。相关的研究论文于9月16日在线发表在《Nature Genetics》期刊上

2012年10月《自然-遗传》

中文翻译


【题目】播散性浅表性光化性汗孔角化症中的MVK突变

【译文】播散性浅表性光化性汗孔角化症(DSAP)是一类常染色体显性遗传的表皮角质化异常疾病,但至今DSAP的病因仍不清楚。我们对来自DSAP家族的一名正常个体和两名受累者的样本进行了外显子组测序。在过滤掉已存在的SNP数据库、8个HapMap外显子组和1000个基因组计划数据,且考虑到突变基因的功能意义后,甲羟戊酸激酶基因(MVK)是定位于先前确定的连锁区域内的唯一一个候选基因。本研究对患有家族性DSAP的57名个体和患有散发性DSAP的25名个体进行了桑格测序,结果分别在受累者中鉴定到33%和16%的MVK突变。本研究鉴定到的14个MVK突变均不存在于676个正常个体中。我们对体外培养的原代角质形成细胞进行功能研究,结果表明MVK在调控钙诱导的胶质细胞分化中起到了一定的作用,可能可以保护角质细胞免受A型紫外辐射诱导的细胞凋亡。本研究结果应该有助于促进理解DSAP的发病机理。

英文原稿


[Title]: Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis

[Authors]: 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

[Abstract]: 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.

原文地址

http://www.nature.com/ng/journal/v44/n10/full/ng.2409.html

 

本站声明: 生物文库所有文章欢迎转载,所有文章未说明,均属于原创,转载均请注明出处。
本文链接: http://www.bioku.cn/201212/nature-genetics-dsap-mvk-autosomal-dominantly-inherited-disorder-pathogenesis/
版权所有: 生物文库 - 生物医学、生物技术核心期刊文摘

留言


× 七 = 63


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息