title: Novel mutations in two families with Darier's disease.
abstract: BACKGROUND
  Darier's disease (DD) is an autosomal dominant skin disorder characterized by abnormal keratinization and acantholysis. Deleterious mutations in the gene ATP2A2 which encodes SERCA2, a calcium pump of the sarco/endoplasmic reticulum underlie the disease.
  
  
  OBJECTIVE
  To identify the genetic defect in two Jewish families of eastern-European ancestry with DD.
  
  
  METHODS
  DNA was extracted from peripheral blood of six patients and three healthy members of the two families. Polymerase chain reaction (PCR) was carried out to amplify the exons and flanking intron boundaries of the ATP2A2 gene followed by direct sequencing. Restriction fragment analysis verified the presence or absence of the mutations. Results Two novel mutations were identified. A nonsense mutation, a change of C391 to T (R131X) in exon 5, was found in one family and a missense mutation, a change of A530 to C (Q177P) in the second. The mutations were not present in 50 healthy individuals of the same ethnic origin. Both pathogenic mutations are in codons that are located in a highly conserved cytoplasmic beta-strand domain which functions as the transduction site.
  
  
  CONCLUSIONS
  The existence of two mutations in two Jewish families of the same ancestry might confirm the previously published reports that most mutations in that gene are private.
authors.affiliation: Department of Dermatology, Huzot Clinic of Clalit Health Services, Ashkelon, Israel. boazam@clalit.org.il
authors.forename: B
authors.initials: B
authors.lastname: Amichai
authors.forename: M
authors.initials: M
authors.lastname: Karpati
authors.forename: B
authors.initials: B
authors.lastname: Goldman
authors.forename: L
authors.initials: L
authors.lastname: Peleg
mesh_terms: D000328:Adult; D018389:Codon, Nonsense; D007644:Darier Disease / Q000208:ethnology / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007585:Jews / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases