2. Academic Validation
  3. Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis

Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis

  • Nat Genet. 2012 Oct;44(10):1156-60. doi: 10.1038/ng.2409.
Sheng-Quan Zhang 1,  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
Affiliations

Affiliation

  • 1 Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China.
PMID: 22983302 DOI: 10.1038/ng.2409
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.

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