An <i>ATP2A2</i> Missense Mutation in a Japanese Family with Darier Disease: A Case Report and Review of the Japanese Darier Disease Patients with <i>ATP2A2</i> Mutations

Abstract

Darier disease (DD) is a rare autosomal dominant skin disorder due to mutations in the ATP2A2 gene, which encodes sarco/endoplasmic reticulum Ca 2+ ATPase isoform 2 (SERCA2). The clinical manifestations of DD are characterized by warty papules and plaques in seborrheic areas, and association with neuropsychiatric abnormalities has also been reported in a few families with DD. We herein report a classic Japanese DD case with a previously described mutation (p.C560R) in ATP2A2. In Japan, 26 mutations in the ATP2A2 gene in 7 pedigrees and 19 sporadic cases with DD have been reported, among which one pedigree and one sporadic case were accompanied by neuropsychiatric symptoms. A review of the reports confirmed that most mutations were of the missense type and no consistent genotypephenotype correlations were found. (J Nippon Med Sch 2017; 84: 246 250)

Heterozygous ATP2A2 missense variant identified in a Shih Tzu with Darier disease

“…Skin lesions may be triggered by environmental factors such as heat, sweating, sunlight, and stress. Disease onset in human patients is highly variable with reports ranging from age 3 to 75 years, but most frequently starts around puberty and usually before the third decade (Foggia & Hovnanian, 2004; Li et al, 2017; Nellen et al, 2017). Clinical signs in the previously reported Irish Terrier with Darier disease started with a lesion in the ear canal and subsequent ear infection at age 4 months (Linek et al, 2020).…”

“…However, the ATP2A2 protein is highly conserved across vertebrates and missense variants in the same region of the protein have been reported in human patients with Darier disease, e.g. p.N796S or p.A838P (Li et al, 2017; Nellen et al, 2017). The highly characteristic phenotype and the finding of a missense variant in the only known functional candidate gene mutually support the diagnosis of Darier disease in the studied dog.…”

A novel mutation in exon 1 of the ATP2A2 gene in four members of one Chinese family with Darier disease

“…The prevalence of DD has been reported at 1 in 60 000-90 000, 1 and onset is usually in adolescence. Histologically we see loss of adhesion between epidermal cells leading to abnormal keratinization and suprabasal cleavage.…”