Mendelian Disorders of Cornification Caused by Defects in Intracellular Calcium Pumps: Mutation Update and Database for Variants in ATP2A2 and ATP2C1 Associated with Darier Disease and Hailey-Hailey Disease

Ruud G. L. Nellen*, Peter M. Steijlen, Maurice A. M. van Steensel, Maaike Vreeburg, Jorge Frank, Michel van Geel, European Professional Contributors

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

33 Citations (Web of Science)

Abstract

The two disorders of cornification associated with mutations in genes coding for intracellular calcium pumps are Darier disease (DD) and Hailey-Hailey disease (HHD). DD is caused by mutations in the ATP2A2 gene, whereas the ATP2C1 gene is associated with HHD. Both are inherited as autosomal-dominant traits. DD is mainly defined by warty papules in seborrheic and flexural areas, whereas the major symptoms of HHD are vesicles and erosions in flexural skin. Both phenotypes are highly variable. In 12%-40% of DD patients and 12%-55% of HHD patients, no mutations in ATP2A2 or ATP2C1 are found. We provide a comprehensive review of clinical variability in DD and HHD and a review of all reported mutations in ATP2A2 and ATP2C1. Having the entire spectrum of ATP2A2 and ATP2C1 variants allows us to address the question of a genotype-phenotype correlation, which has not been settled unequivocally in DD and HHD. We created a database for all mutations in ATP2A2 and ATP2C1 using the Leiden Open Variation Database (LOVD v3.0), for variants reported in the literature and future inclusions. This data may be of use as a reference tool in further research on treatment of DD and HHD. (C) 2016 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)343-356
Number of pages14
JournalHuman Mutation
Volume38
Issue number4
DOIs
Publication statusPublished - Apr 2017

Keywords

  • Darier disease
  • Hailey-Hailey disease
  • acrokeratosis verruciformis of Hopf
  • ATP2A2
  • ATP2C1
  • SERCA2
  • SPCA1
  • locus-specific database
  • genotype-phenotype correlation
  • RETICULUM CA2+-ATPASE MUTANTS
  • ISRAEL COMBINED EVALUATION
  • HUMAN INHERITED DISEASE
  • CHINESE PATIENTS
  • ACROKERATOSIS VERRUCIFORMIS
  • CLINICAL-FEATURES
  • CA2+ PUMP
  • NEUROPSYCHIATRIC ASPECTS
  • CULTURED KERATINOCYTES
  • MISSENSE MUTATION

Cite this