Molecular confirmation of founder mutation c.-167A>G in Tunisian patients with PMLD disease.

Gene

PubMedID: 23142375

Kammoun Jellouli N, Salem IH, Ellouz E, Louhichi N, Tlili A, Kammoun F, Triki C, Fakhfakh F, Tunisian network on mental retardation study. Molecular confirmation of founder mutation c.-167A>G in Tunisian patients with PMLD disease. Gene. 2013;513(2):233-8.
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.