title: Mutational founder effect in recessive dystrophic epidermolysis bullosa families from Southern Tunisia.
abstract: Dystrophic epidermolysis bullosa (DEB) is a group of heritable bullous skin disorders caused by mutations in the COL7A1 gene. One of the most severe forms of DEB is the severe generalized [recessive dystrophic epidermolysis bullosa (RDEB-SG)] subtype, which is inherited in an autosomal recessive manner. This subtype is most often due to COL7A1 mutations resulting in a premature termination codon on both alleles. We report here, the molecular investigation of 15 patients belonging to 14 nuclear families from the city of Sfax in Southern Tunisia, with clinical features of RDEB-SG complicated by squamous cell carcinoma in 3 patients. We identified two novel mutations, p.Val769LeufsX1 and p.Ala2297SerfsX91, in addition to one previously reported mutation (p.Arg2063Trp). The p.Val769LeufsX1 mutation was shared by 11 families and haplotype analysis indicated that it is a founder mutation. The p.Ala2297SerfsX91 mutation was a private mutation found in only one family. Together with the previously described recurrent mutations in Tunisia, screening for the founder p.Val769LeufsX1 mutation should provide a rapid molecular diagnosis tool for mutation screening in RDEB patients from Southern Tunisia and possibly from other Mediterranean populations sharing the same genetic background.
authors.affiliation: Biomedical Genomics and Oncogenetics Laboratory (LR11IPT 05), Institut Pasteur de Tunis, Université El Manar de Tunis, 13, Place Pasteur, BP74, 1002, Tunis, Tunisia.
authors.forename: Ahlem Sabrine
authors.initials: AS
authors.lastname: Ben Brick
authors.forename: Nadia
authors.initials: N
authors.lastname: Laroussi
authors.forename: Hela
authors.initials: H
authors.lastname: Mesrati
authors.forename: Rym
authors.initials: R
authors.lastname: Kefi
authors.forename: Mbarka
authors.initials: M
authors.lastname: Bchetnia
authors.forename: Khaled
authors.initials: K
authors.lastname: Lasram
authors.forename: Nizar
authors.initials: N
authors.lastname: Ben Halim
authors.forename: Lilia
authors.initials: L
authors.lastname: Romdhane
authors.forename: Houyem
authors.initials: H
authors.lastname: Ouragini
authors.forename: Salaheddine
authors.initials: S
authors.lastname: Marrakchi
authors.forename: Mohamed Samir
authors.initials: MS
authors.lastname: Boubaker
authors.forename: Mounira
authors.initials: M
authors.lastname: Meddeb Cherif
authors.forename: Daniele
authors.initials: D
authors.lastname: Castiglia
authors.forename: Alain
authors.initials: A
authors.lastname: Hovnanian
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.forename: Hamida
authors.initials: H
authors.lastname: Turki
mesh_terms: D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000150:complications; D018389:Codon, Nonsense / Q000235:genetics; D024143:Collagen Type VII / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000473:pathology; D005260:Female; D018703:Founder Effect; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D012867:Skin / Q000473:pathology; D014416:Tunisia
chemical_list: C569053:COL7A1 protein, human; D018389:Codon, Nonsense; D024143:Collagen Type VII