Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis

Nat Genet. 2012 Oct;44(10):1156-60. doi: 10.1038/ng.2409. Epub 2012 Sep 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Case-Control Studies
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • DNA Mutational Analysis
  • Exome*
  • Female
  • Genetic Association Studies
  • Humans
  • Keratinocytes / physiology
  • Male
  • Pedigree
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Point Mutation*
  • Porokeratosis / genetics*
  • Porokeratosis / pathology
  • RNA Splice Sites


  • RNA Splice Sites
  • Phosphotransferases (Alcohol Group Acceptor)
  • mevalonate kinase