title: Congenital lamellar ichthyosis in Tunisia is caused by a founder nonsense mutation in the TGM1 gene.
abstract: Lamellar ichthyosis (LI, MIM# 242300) is a severe autosomal recessive genodermatosis present at birth in the form of collodion membrane covering the neonate. Mutations in the TGM1 gene encoding transglutaminase-1 are a major cause of LI. In this study molecular analysis of two LI Tunisian patients revealed a common nonsense c.788G>A mutation in TGM1 gene. The identification of a cluster of LI pedigrees carrying the c.788G>A mutation in a specific area raises the question of the origin of this mutation from a common ancestor. We carried out a haplotype-based analysis by way of genotyping 4 microsatellite markers and 8 SNPs flanking and within the TGM1 gene spanning a region of 6 Mb. Haplotype reconstruction from genotypes of all members of the affected pedigrees indicated that all carriers for the mutation c.788G>A harbored the same haplotype, indicating common ancestor. The finding of a founder effect in a rare disease is essential for the genetic diagnosis and the genetic counselling of affected LI pedigrees in Tunisia.
authors.affiliation: Human Molecular Genetic Laboratory, Faculty of Medicine of Sfax, Avenue Magida Boulila, 3029, Sfax, Tunisia. nacim.louhichi@gmail.com
authors.forename: Nacim
authors.initials: N
authors.lastname: Louhichi
authors.forename: Ikhlass
authors.initials: I
authors.lastname: Hadjsalem
authors.forename: Slaheddine
authors.initials: S
authors.lastname: Marrakchi
authors.forename: Fatma
authors.initials: F
authors.lastname: Trabelsi
authors.forename: Abderrahmen
authors.initials: A
authors.lastname: Masmoudi
authors.forename: Hamida
authors.initials: H
authors.lastname: Turki
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D000293:Adolescent; D018389:Codon, Nonsense; D003241:Consanguinity; D005260:Female; D018703:Founder Effect; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011503:Transglutaminases / Q000235:genetics*; D014416:Tunisia; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D011503:Transglutaminases; C105804:transglutaminase 1