Darier (Darier-White) disease (DD) is an autosomal dominant skin disorder caused by pathogenic mutations in the ATP2 A 2 gene which encodes a calcium ATPase in the sarco-endoplasmic reticulum (SERCA2). Defects in the SERCA2 protein lead to an impairment of cellular calcium homeostasis, which in turn, triggers cell death path-ways. There is a high prevalence of neuropsychiatric disorders in patients affected by this condition, namely intellectual disability, bipolar disorder, schizophrenia, and suicidality. Though these associations have been well-documented over the years, little has been discussed or investigated regarding the pathophysiological mecha-nisms. The goal of this article is to review the literature related to the most com-monly associated neuropsychiatric disorders found in patients with DD, highlight the pathophysiological mechanisms underlying each condition, and examine potential in-terventions that may be of interest for future development. A literature search was performed using PubMed to access and review relevant articles published in the last 40 years. Keywords searched included Darier disease neuropsychiatric, Darier disease pathophysiology, SERCA2 central nervous system, SERCA 2 skin, ATP2A2 central nervous system, ATP2A2 skin, sphingosine-1- phosphate signalling skin, sphingosine-1- phosphate signalling central nervous system, P2X7 receptor skin, and P2X7 recep-tor central nervous system. Our search resulted in 2692 articles, of which 61 articles were ultimately included in this review.
calcium signalling, Darier disease, neuropsychiatric disorders, SERCA2
Ambur A, Zaidi A, Dunn C, Nathoo R. Impaired Calcium Signalling and Neuropsychiatric Disorders in Darier Disease: An Exploratory Review. Experimental Dermatology. 2022; 31(9). doi: 10.1111/exd.14642.