OBJECTIVE: To study the mutation spectrum and phenotype-genotype correlation of Darier disease (DD) in Tunisian patients. DESIGN: Case series. SETTING: Referral center: Department of Dermatology (La Rabta Hospital), Tunis, Tunisia. PATIENTS: Eight large Tunisian families with DD, with a total of 23 patients and 9 unaffected family members. MAIN OUTCOME MEASURE: 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.
OBJECTIVE: To study the mutation spectrum and phenotype-genotype correlation of Darier disease (DD) in Tunisian patients. DESIGN: Case series. SETTING: Referral center: Department of Dermatology (La Rabta Hospital), Tunis, Tunisia. PATIENTS: Eight large Tunisian families with DD, with a total of 23 patients and 9 unaffected family members. MAIN OUTCOME MEASURE: 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.