title: Darier disease in Slovenia: spectrum of ATP2A2 mutations and relation to patients' phenotypes.
abstract: ATP2A2 encodes the sarco/endoplasmic reticulum Ca2+- ATPase (SERCA2) and has been identified as a defective gene in Darier disease (DD). It is an autosomal dominant genodermatosis, which is characterized by loss of adhesion between suprabasal epidermal keratinocytes (acantholysis) and abnormal keratinization (dyskeratosis). We examined 28 Slovenian patients with DD (the cohort of patients represents over 50% of all DD patients in Slovenia) and screened genomic DNA for ATP2A2 mutations and RNA for splice site mutations. We identified 7 different ATP2A2 mutations, 4 of which are novel: A516P, R559G, 544+1del6, and 1762-6del18. We also found two previously described polymorphisms 2741+54 G>A in intron XVIII and 2172 G>A (A724A) in exon 15, with allele frequencies of 64.2% and 11.3%, respectively. The mutations are scattered throughout the gene and affect the actuator, phosphorylation, stalk and transmembrane domains of SERCA2. A P160L mutation in a Slovene patient with severe DD and a history of deafness is another consistent genotype-phenotype correlation. It seems that mutations of the ATP2A2 gene may also play a role in the pathogenesis of deafness, which seems to be a new phenotypic characteristic of DD patients.
authors.affiliation: Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Korytkova 2, SI-1000, Slovenia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Godic
authors.forename: Mojca
authors.initials: M
authors.lastname: Strazisar
authors.forename: Andrej
authors.initials: A
authors.lastname: Zupan
authors.forename: Branka
authors.initials: B
authors.lastname: Korosec
authors.forename: Aleksej
authors.initials: A
authors.lastname: Kansky
authors.forename: Damjan
authors.initials: D
authors.lastname: Glavac
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D007644:Darier Disease / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012313:RNA / Q000235:genetics*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000097:blood / Q000235:genetics*; D017524:Slovenia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D012313:RNA; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human