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Four novel ATP2A2 mutations in Slovenian patients with Darier disease

Aleksandar Godic1, Branka Korosec, Jovan Miljković

  • 1Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. aleksandar.godic@gmail.com

Journal of the American Academy of Dermatology
|March 13, 2010
PubMed
Abstract

Insights

Darier disease (DD) is a genetic skin disorder caused by ATP2A2 gene mutations. This study identified four novel mutations in Slovenian patients and suggests deafness may be a new characteristic of DD.

Area of Science:

  • Genetics
  • Dermatology
  • Molecular Biology

Background:

  • Darier disease (DD) is an autosomal dominant genodermatosis linked to ATP2A2 gene mutations.
  • Keratinocyte calcium (Ca2+) store depletion impacts cell cycle regulation and differentiation.
  • Accumulated DNA damage and secondary mutations can lead to clonal proliferation in DD lesions.

Purpose of the Study:

  • To conduct a clinical, demographic, and genetic analysis of Slovenian Darier disease patients.
  • To characterize the ATP2A2 mutations present in the Slovenian DD cohort.
  • To investigate potential new phenotypic features associated with DD.

Main Methods:

  • Examined 28 Slovenian patients diagnosed with Darier disease.
  • Screened genomic DNA for ATP2A2 gene mutations.
  • Analyzed RNA for splice site mutations.

Main Results:

  • Estimated Darier disease prevalence in Slovenia at 2.7/100,000.
  • Identified 7 distinct ATP2A2 mutations, including 4 novel ones (A516P, R559G, 463-6del6, 1762-6del18).
  • Observed a history of perceptive deafness in two families with DD, suggesting a potential new phenotype.

Conclusions:

  • Four novel ATP2A2 mutations were identified in Slovenian Darier disease patients.
  • Deafness appears to be a newly recognized phenotypic characteristic associated with Darier disease.
  • Further in vitro studies on SERCA2 expression and Ca2+ uptake are recommended to understand desmosomal assembly in DD.

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