Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis
| Autor: | Ping Li, Yantao Ding, Xuejun Zhang, Jinping Gao, Liangdan Sun, Min Li, Kun Xia, You-Wen Zhou, Xin Zhang, Bo Liang, Jian Wang, Pan Li, Yuan Liu, Yingrui Li, Wen Wang, Xiaodong Zheng, Ming Zeng, Ke Yang, Pei-Guang Wang, Jianjun Liu, Tingting He, Jun Zhu, Sheng-Quan Zhang, Bi-Rong Guo, Hui Li, Gang Chen, Fusheng Zhou, Jingchu Hu, Jun-Sheng Hou, Guangqing Sun, Hui Cheng, Xing Fan, Xin Hu, Xianyong Yin, Yujun Sheng, Huanming Yang, Feng-Li Xiao, Xiang-Feng Yuan, Sen Yang, Shi-Xiang Zhao, Wei-Dong Du, Yu-Juan Zhai, Tao Jiang, Zhen-Ying Wang, Jun Wang, Zhong-Yi Yu, Zheng-Mao Hu, Li Zhang, Songke Shen, Wei-Wei Ha, Huayang Tang, Wen Ju Wang, Hui-Feng Zhang, Yong Cui, Bao-Yu Wu, Yu Xu, Xianfa Tang, Jian-Bo Wang, Yang Li, Yunqing Ren, Jing Wang, Shengcai Wei, Min Gao, Fang-Fang Qian, Jie Wang, Xianbo Zuo, Shengxiu Liu |
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| Rok vydání: | 2012 |
| Předmět: |
Keratinocytes
Male Candidate gene DNA Mutational Analysis Apoptosis Disseminated superficial actinic porokeratosis symbols.namesake Genetics medicine Humans Point Mutation Exome 1000 Genomes Project Cells Cultured Genetic Association Studies Exome sequencing Cell Proliferation Sanger sequencing biology Point mutation Mevalonate kinase Cell Differentiation medicine.disease Pedigree Porokeratosis Phosphotransferases (Alcohol Group Acceptor) Case-Control Studies symbols biology.protein Female RNA Splice Sites |
| Zdroj: | Nature Genetics. 44:1156-1160 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.2409 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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