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.

Identification of a Novel Mutation ofLAMB3Gene in a Lybian Patient with Hereditary Epidermolysis Bullosa by Whole Exome Sequencing

“…Direct sequencing of all COL7A1 coding regions might be challenging as they encompass 118 exons, and more than 70 polymerase chain reaction primer pairs are necessary for the amplification of all coding regions3. In addition, the genetic heterogeneity and the important number of “private mutation” make the genetic diagnosis more challenging even in endogamous populations4. WES has led to the identification of a considerable number of pathogenic mutations in monogenic Mendelian disorders, including skin pathologies5.…”

“…This is to our knowledge the first study of a Libyan patient. Our previous studies showed that despite mutational heterogeneity of HEB, some mutations are likely founder and closed to specific geographic regions4. Therefore, screening of c.2701+1G>A mutation could assist in determining the molecular aetiology of HEB among eastern Libyan patients.…”