title: Molecular confirmation of founder mutation c.-167A>G in Tunisian patients with PMLD disease.
abstract: Pelizaeus Merzbacher disease and Pelizaeus Merzbacher like disease (PMLD) are hypomyelinating leucodystrophies of the central nervous system (CNS) with a very similar phenotype. PMD is an X-linked recessive condition caused by mutations, deletion duplication or triplication of the proteolipid protein 1 gene (PLP1). However, PMLD is a recessive autosomal hypomyelinating leukodystrophy caused by mutations of the GJC2 gene. In this study, we analyzed 5 patients belonging to 4 Tunisian families. Direct sequencing of GJC2 gene in all probands showed the same homozygous founder mutation c.-167A>G localized in the promoter region. We also generated two microsatellite markers GJC2 195GT and GJC2 76AC closed to the GJC2 gene to confirm the presence of a founder effect for this mutation. Haplotype study showed that the c.-167A>G promoter mutation occurred in a specific founder haplotype in Tunisian population. The identification of this founder mutation has important implications towards genetic counseling in relatives of these families and the antenatal diagnosis.
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine. Faculté de Médecine de Sfax Université de Sfax, Tunisia. kammounnad@gmail.com
authors.forename: Nadege
authors.initials: N
authors.lastname: Kammoun Jellouli
authors.forename: Ikhlass Hadj
authors.initials: IH
authors.lastname: Salem
authors.forename: Emna
authors.initials: E
authors.lastname: Ellouz
authors.forename: Nacim
authors.initials: N
authors.lastname: Louhichi
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: tlili
authors.forename: Fatma
authors.initials: F
authors.lastname: Kammoun
authors.forename: Chanez
authors.initials: C
authors.lastname: Triki
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D017630:Connexins / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics*; D010704:Phorbols; D011401:Promoter Regions, Genetic; D014416:Tunisia
chemical_list: D017630:Connexins; D010704:Phorbols; C427305:connexin 47; C470237:pedilstatin