title: New mutations of Darier disease in Tunisian patients.
abstract: Darier's disease (DD, MIM 124200) also known as Darier-White disease and keratosis follicularis, is a rare autosomal dominant skin disorder characterized by warty papules and plaques in the seborrheic area (central trunk, flexures, scalp, and forehead). Pathogenic mutations in the ATP2A2 gene encoding the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) 2 gene underlie the disease. In the present study, we performed genetic investigation of three unrelated Tunisian families affected by DD. Mutation screening was performed by direct sequencing of the coding region and exon/intron boundaries of the ATP2A2 gene. Patients in the 3 studied families exhibited classical DD phenotype. DD was associated with neurological and cardiac disorders in one family. Two novel mutations were identified: a missense mutation (R559Q) and a frameshift mutation (1713-1714 del 2A). Both pathogenic mutations are located in exon 13 of the ATP2A2 gene and affected the ATP-binding site of the SERCA2 protein. In one family, no mutation was found within the coding region and exon/intron boundaries of the ATP2A2 gene. Our findings provide further evidence for the genetic heterogeneity of DD in Tunisia and that most mutations involved in this disease are family specific.
authors.affiliation: Molecular Investigation of Genetic Orphan Diseases Research Unit, Institut Pasteur de Tunis, Pasteur, 1002 Tunis Belvédère, Tunisia.
authors.forename: Mbarka
authors.initials: M
authors.lastname: Bchetnia
authors.forename: Rym
authors.initials: R
authors.lastname: Benmously
authors.forename: Ahlem Sabrine
authors.initials: AS
authors.lastname: Ben Brick
authors.forename: Cherine
authors.initials: C
authors.lastname: Charfeddine
authors.forename: Youssef
authors.initials: Y
authors.lastname: Ben Ameur
authors.forename: Mohamed
authors.initials: M
authors.lastname: Fajraoui
authors.forename: Achraf
authors.initials: A
authors.lastname: Debbiche
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ben Ayed
authors.forename: Mourad
authors.initials: M
authors.lastname: Mokni
authors.forename: Samy
authors.initials: S
authors.lastname: Fenniche
authors.forename: Inçaf
authors.initials: I
authors.lastname: Mokhtar
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
mesh_terms: D000328:Adult; D007644:Darier Disease / Q000378:metabolism*; D005260:Female; D006801:Humans; D009154:Mutation; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human