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Updated: May 17, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Molecular confirmation of founder mutation c.-167A>G in Tunisian patients with PMLD disease
Nadege Kammoun Jellouli1, Ikhlass Hadj Salem, Emna Ellouz
1Laboratoire de Génétique Moléculaire Humaine. Faculté de Médecine de Sfax Université de Sfax, Tunisia. kammounnad@gmail.com
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.
Insights
Researchers identified a specific founder mutation in the GJC2 gene promoter in Tunisian families with Pelizaeus-Merzbacher-like disease (PMLD). This discovery aids genetic counseling and prenatal diagnosis for this rare neurological disorder.
Area of Science:
- Neurogenetics
- Molecular Genetics
- Human Genetics
Background:
- Pelizaeus-Merzbacher disease (PMD) and Pelizaeus-Merzbacher-like disease (PMLD) are severe hypomyelinating leukodystrophies affecting the central nervous system (CNS).
- PMD is X-linked, caused by PLP1 gene mutations, while PMLD is autosomal recessive, linked to GJC2 gene mutations.
- Both conditions present with similar neurological phenotypes, making accurate genetic diagnosis crucial.
Purpose of the Study:
- To investigate the genetic basis of PMLD in Tunisian families.
- To identify specific mutations within the GJC2 gene.
- To determine the prevalence and origin of identified mutations within the population.
Main Methods:
- Genetic analysis of 5 patients from 4 Tunisian families.
- Direct sequencing of the GJC2 gene to identify mutations.
- Generation of microsatellite markers (GJC2 195GT and GJC2 76AC) to confirm founder effect.
- Haplotype analysis to trace the mutation's origin.
Main Results:
- A homozygous founder mutation, c.-167A>G, was identified in the GJC2 gene promoter region in all analyzed patients.
- This mutation was consistently found on a specific founder haplotype within the Tunisian population.
- The identified mutation explains the PMLD phenotype in these families.
Conclusions:
- A founder mutation in the GJC2 promoter is responsible for PMLD in these Tunisian families.
- This finding is significant for genetic counseling and prenatal diagnosis for affected relatives.
- Understanding founder mutations aids in diagnosing and managing rare genetic diseases in specific populations.
