title: Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis.
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.
authors.affiliation: Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Sheng-Quan
authors.initials: SQ
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Ren
authors.forename: Sheng-Cai
authors.initials: SC
authors.lastname: Wei
authors.forename: Liang-Dan
authors.initials: LD
authors.lastname: Sun
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Xian-Yong
authors.initials: XY
authors.lastname: Yin
authors.forename: Zheng-Mao
authors.initials: ZM
authors.lastname: Hu
authors.forename: Zhen-Ying
authors.initials: ZY
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Bi-Rong
authors.initials: BR
authors.lastname: Guo
authors.forename: Hua-Yang
authors.initials: HY
authors.lastname: Tang
authors.forename: Xian-Fa
authors.initials: XF
authors.lastname: Tang
authors.forename: Yan-Tao
authors.initials: YT
authors.lastname: Ding
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Bao-Yu
authors.initials: BY
authors.lastname: Wu
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Xiang-Feng
authors.initials: XF
authors.lastname: Yuan
authors.forename: Jun-Sheng
authors.initials: JS
authors.lastname: Hou
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Ha
authors.forename: Wen-Ju
authors.initials: WJ
authors.lastname: Wang
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Zhai
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Qian
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Zuo
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zheng
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Sheng
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Gao
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.forename: Pan
authors.initials: P
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Feng-Li
authors.initials: FL
authors.lastname: Xiao
authors.forename: Pei-Guang
authors.initials: PG
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Sheng-Xiu
authors.initials: SX
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Xing
authors.initials: X
authors.lastname: Fan
authors.forename: Song-Ke
authors.initials: SK
authors.lastname: Shen
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: Guang-Qing
authors.initials: GQ
authors.lastname: Sun
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.forename: Jing-Chu
authors.initials: JC
authors.lastname: Hu
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: He
authors.forename: Ying-Rui
authors.initials: YR
authors.lastname: Li
authors.forename: Huan-Ming
authors.initials: HM
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Zhong-Yi
authors.initials: ZY
authors.lastname: Yu
authors.forename: Hui-Feng
authors.initials: HF
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Shi-Xiang
authors.initials: SX
authors.lastname: Zhao
authors.forename: You-Wen
authors.initials: YW
authors.lastname: Zhou
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Du
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D015603:Keratinocytes / Q000502:physiology; D008297:Male; D010375:Pedigree; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D017354:Point Mutation; D017499:Porokeratosis / Q000235:genetics* / Q000473:pathology; D022821:RNA Splice Sites
chemical_list: D022821:RNA Splice Sites; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase