title: A novel missense mutation in the gene encoding SLURP-1 in patients with Mal de Meleda from northern Tunisia.
abstract: BACKGROUND
  Mal de Meleda (MDM) is a rare autosomal recessive skin disorder which belongs to the clinically and genetically heterogeneous group of palmoplantar keratodermas (PPK). Clinically, MDM is characterized by erythema and hyperkeratosis of the palms and soles with sharp demarcation that appears soon after birth and progressively extends to the dorsal surface of the hands and feet.
  
  
  OBJECTIVE
  Except for the molecular study reported in Algerian families, MDM has not yet been investigated in the Maghrebian population, characterized by its heterogeneous ethnic background and a high rate of consanguinity. In this study we report genetic and molecular investigations of eight unrelated consanguineous Tunisian families including 17 affected individuals.
  
  
  METHODS
  Eight large consanguineous MDM families who originated from cities of northern Tunisia, with a total of 17 patients and 22 unaffected family members were investigated. Families were genotyped with the following microsatellite markers: CNG003, D8S1751 and D8S1836. Mutation analyses were performed in affected patients, in both parents and in unaffected individuals. Linkage analysis was also performed.
  
  
  RESULTS
  All the clinical features of MDM were constantly present. Nevertheless variable severity was noted among patients. Histological details were recorded. The haplotype analysis of markers CNG003, D8S1751 and D8S1836 revealed that all affected offspring were homozygous by descent for the three polymorphic markers. The maximum lod score value, 3.22, confirmed the evidence for linkage to the ARS gene. Three haplotypes were observed, and the findings suggest that at least three different mutations within the ARS gene segregate with these haplotypes. Three different mutations were identified, the 82delT mutation previously described and two novel missense mutations.
  
  
  CONCLUSIONS
  The results suggest that the ARS gene is likely to be responsible for MDM in the eight Tunisian families. The clinical variability in the expression of PPK in MDM Tunisian patients might be accounted for by the intervention of modifier genes influencing the MDM phenotype.
authors.affiliation: Laboratoire d'Immunologie, Vaccinologie et Génétique Moléculaire, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur, 1002 Tunis Belvédère, Tunisia.
authors.forename: C
authors.initials: C
authors.lastname: Charfeddine
authors.forename: M
authors.initials: M
authors.lastname: Mokni
authors.forename: R
authors.initials: R
authors.lastname: Ben Mousli
authors.forename: R
authors.initials: R
authors.lastname: Elkares
authors.forename: C
authors.initials: C
authors.lastname: Bouchlaka
authors.forename: S
authors.initials: S
authors.lastname: Boubaker
authors.forename: S
authors.initials: S
authors.lastname: Ghedamsi
authors.forename: D
authors.initials: D
authors.lastname: Baccouche
authors.forename: A
authors.initials: A
authors.lastname: Ben Osman
authors.forename: K
authors.initials: K
authors.lastname: Dellagi
authors.forename: S
authors.initials: S
authors.lastname: Abdelhak
mesh_terms: D000950:Antigens, Ly / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007223:Infant; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D014416:Tunisia; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
chemical_list: D000950:Antigens, Ly; D005819:Genetic Markers; C048963:SLURP1 protein, human; D014568:Urokinase-Type Plasminogen Activator