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.
Darier disease (DD) and Hailey-Hailey disease (HHD) are autosomal dominantly inherited genodermatosis, caused by mutations in ATP2A2 gene and ATP2C1 respectively.
The results suggest that modulation of ATP2A2 and ATP2C1 mRNA expression by UV or cytokines might contribute to the clinical presentations unique to DD and HHD, and that the controlled expression of these genes plays an important role in keratinocyte homeostasis, function and differentiation.
Darier's disease (DD) and Hailey-Hailey disease (HHD) are skin disorders arising, respectively, from autosomal dominant mutations in ATP2A2, encoding the sacro/endoplasmic reticulum calcium ATPase, and ATP2C1, encoding the Golgi apparatus calcium ATPase.
This study demonstrates that defects in ATP2C1 cause HHD and together with the recent identification of ATP2A2 as the defective gene in Darier's disease, provide further evidence of the critical role of Ca(2+)signaling in maintaining epidermal integrity.