Three-base deletion mutation c.120_122delGTT inATP2A2leads to the unique phenotype of comedonal Darier disease

Abstract

Darier disease (DD; Darier―White disease; OMIM 124200) is an autosomal dominant inherited disorder. 1 Clinically, it is characterized by recurrent and multiple hyperkeratotic papules or nodules affecting the trunk and flexural aspects of the extremities. 1 Characteristic histopathological features are dyskeratotic cells in the form of corps ronds and grains, suprabasal acantholysis forming suprabasal lacunae and irregular upward proliferation into the lacunae of papillae lined with a single layer of basal cells, the so-called villi. 2 The causative gene is ATP2A2 (OMIM 108740) on chromosome 12, which encodes the sarco/endoplasmic reticulum calcium pump ATPase (SERCA2). 2 Clinical variants include the hypertrophic, vesiculobullous, hypopigmented, cornifying, zosteriform and linear subtypes, and the rare subtype comedonal Darier disease (CDD). 1,3―6 CDD tends to appear in seborrhoeic areas. The characteristic morphological features are prominent follicular involvement, sometimes associated with keratotic plugs, and the presence of greatly elongated dermal villi and papillary projections. 4 There have been no conclusive reports on the aetiology of CDD and it is still controversial as to whether or not CDD is a variant of DD, and if it is caused by ATP2A2 gene mutations, although a combination of CDD and classic DD was reported in one patient. 7 The present study identifies a previously unreported three-base deletion mutation in ATP2A2 in a patient with CDD.