Darier Disease - A Multi-organ Condition?

Abstract

Darier disease is a severe, rare autosomal dominant inherited skin condition caused by mutations in the ATP2A2 gene encoding sarcoendoplasmic reticulum Ca2+-ATPase isoform 2 in the endoplasmic reticulum. Since sarcoendoplasmic reticulum Ca2+-ATPase isoform 2 is expressed in most tissues, and intracellular calcium homeostasis is of fundamental importance, it is conceivable that other organs besides the skin may be involved in Darier disease. This review focusses on the association of Darier disease with other organ dysfunctions and diseases, emphasizing their common molecular pathology. In conclusion, Darier disease should be considered a systemic condition that requires systemic and disease mechanism targeted treatments.

Keywords: SERCA2; calcium; endoplasmic reticulum; genodermatosis; rare disease; Darier disease.

Fig. 1

Patient with typical Darier disease, with cutaneous red papules that coalesce into plaques. Black square: inset magnified area. Patient consent for publication was given.

Fig. 2

(A) Endoplasmic reticulum in a human keratinocyte as seen by transmission electron microscopy. ER: endoplasmic reticulum; M: mitochondrion; K: keratin; N: nucleus. (B) Principles of calcium homeostasis in the endoplasmic reticulum. SERCA1-3 pumps Ca²⁺ into the ER, while the channels ryanodine receptor (RyR) and inositol trisphosphate receptor (IP3R) releases Ca²⁺ from the ER. The Ca²⁺ concentration is substantially higher in the ER than in the cytosol. Adapted from (182).

Fig. 3

Overview of emerging systemic extracutaneous involvement in Darier disease.