title: Clinical and mutational heterogeneity of Darier disease in Tunisian families.
abstract: OBJECTIVE
  To study the mutation spectrum and phenotype-genotype correlation of Darier disease (DD) in Tunisian patients.
  
  
  METHODS
  Case series.
  
  
  METHODS
  Referral center: Department of Dermatology (La Rabta Hospital), Tunis, Tunisia.
  
  
  METHODS
  Eight large Tunisian families with DD, with a total of 23 patients and 9 unaffected family members.
  
  
  METHODS
  Patients were investigated at the clinical, histological, and genetic levels. Families were genotyped with 5 microsatellite markers spanning the ATP2A2 gene. Mutation screening was performed by direct sequencing of the coding region and exon/intron boundaries of the ATP2A2 gene.
  
  
  RESULTS
  Typical clinical features of DD were constantly present. Phenotypic variation within and between the studied families was observed. Different neuropsychiatric disorders were seen in 5 families, and various cutaneous and extracutaneous original clinical associations were observed. The haplotype analysis led to the identification of different haplotypes cosegregating with the disease in the studied families. Mutation screening of the ATP2A2 gene revealed 3 recurrent mutations (119-120delAG, R677X, and D702N) and 4 novel variations: 2 missense mutations (G217A and L900R), one microinsertion (2772-2779 ins C), and one microdeletion (1747-1749 del 2T).
  
  
  CONCLUSIONS
  Our findings provide evidence for clinical and mutational heterogeneity of Tunisian families with DD. No obvious phenotype-genotype correlation was established. To our knowledge, this is the first molecular investigation of DD in the North African population.
authors.affiliation: Molecular Investigation of Genetic Orphan Diseases Research Unit and Department of Pathology, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: Mbarka
authors.initials: M
authors.lastname: Bchetnia
authors.forename: Cherine
authors.initials: C
authors.lastname: Charfeddine
authors.forename: Selma
authors.initials: S
authors.lastname: Kassar
authors.forename: Hela
authors.initials: H
authors.lastname: Zribi
authors.forename: Haifa Tounsi
authors.initials: HT
authors.lastname: Guettiti
authors.forename: Feten
authors.initials: F
authors.lastname: Ellouze
authors.forename: Mejda
authors.initials: M
authors.lastname: Cheour
authors.forename: Samir
authors.initials: S
authors.lastname: Boubaker
authors.forename: Amel Dhahri-Ben
authors.initials: AD
authors.lastname: Osman
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.forename: Mourad
authors.initials: M
authors.lastname: Mokni
mesh_terms: D000252:Calcium-Transporting ATPases / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D007644:Darier Disease / Q000175:diagnosis / Q000235:genetics*; D003906:Developing Countries; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012494:Sampling Studies; D014416:Tunisia / Q000453:epidemiology
chemical_list: D000252:Calcium-Transporting ATPases