title: Identification of mutations in the ATP2A2 gene in patients with Darier's disease from Hungary.
abstract: Mutation analysis in the ATP2A2 gene had been performed in eight Hungarian patients with Darier's disease (DD), to get more information about phenotype-genotype relations. All patients had moderate to severe skin symptoms. Polymerase chain reaction (PCR) amplification of the entire coding region of ATP2A2 was performed. Mutation detection strategies included heteroduplex scanning by conformation-sensitive gel electrophoresis (CSGE) and direct nucleotide sequencing. We found distinct, heterozygous mutations (five missense, one nonsense, one deletion, and one insertion), six of which were novel. In a 31-year-old DD woman with learning difficulties we disclosed a previously described missense mutation (D702N) in exon 15. A 44-year-old DD woman had a novel T insertion at nucleotide 559 in exon 7 of the ATP2A2 gene, which resulted in a premature termination codon (PTC) at codon 192. A woman, whose skin symptoms developed unusually late, at the age 50, had a new T deletion (1320delT) in exon 11 resulting in a PTC at codon 448. Our most severe case had a known missense mutation N39T, resulting in a non-conservative amino acid change at the upstream stalk region. Three new missense mutations (A161D, R164S, and Q790P) affected conservative regions of the SERCA2 protein within the activation (A)-domain and the M6 transmembrane region. A further new nonsense mutation (C909X) was detected in the M8 transmembrane domain. Our data suggest that differences in DD phenotypes are probably also related to factors different from the type of causative mutation.
authors.affiliation: Semmelweis University, Department of Dermato-Venereology, Budapest, Hungary. raczem@bor.sote.hu
authors.forename: E
authors.initials: E
authors.lastname: Rácz
authors.forename: M
authors.initials: M
authors.lastname: Csikós
authors.forename: Z
authors.initials: Z
authors.lastname: Kornsée
authors.forename: A
authors.initials: A
authors.lastname: Horváth
authors.forename: S
authors.initials: S
authors.lastname: Kárpáti
mesh_terms: D000293:Adolescent; D000328:Adult; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D007644:Darier Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D006814:Hungary; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012867:Skin / Q000473:pathology
chemical_list: D018389:Codon, Nonsense; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D000252:Calcium-Transporting ATPases