Rare Variants Cause Charcot-Marie-Tooth Disease in Malian Families

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Charcot-Marie-Tooth disease (CMT) is a heterogeneous inherited peripheral neuropathy with over 100 identified genes.
• Next-generation sequencing (NGS) has advanced CMT molecular diagnosis, but data from sub-Saharan African (SSA) populations remain limited.

Purpose of the Study:

• To identify rare Charcot-Marie-Tooth disease (CMT) variants in Malian families.
• To expand the understanding of CMT's genetic and clinical spectrum in sub-Saharan Africa.

Main Methods:

• Neurological examinations and Nerve Conduction Studies (NCS) were performed on nine patients from four families.
• Genetic analysis included CMT gene panel testing, whole-exome/genome sequencing, Sanger sequencing, and in silico prediction.
• Variant segregation was assessed in available family members.

Main Results:

• Nine patients exhibited symptoms consistent with CMT, with walking difficulty as the primary complaint.
• Neurological findings included distal muscle weakness, sensory loss, reduced reflexes, and skeletal deformities; some showed ataxic gait.
• Genetic analysis revealed rare pathogenic variants in BSCL2, SH3TC2, and PEX10, and a variant of unknown significance in BAG3.

Conclusions:

• This study reports, for the first time, rare variants in BSCL2, SH3TC2, and PEX10 within sub-Saharan African populations.
• The findings contribute to the global epidemiological, clinical, and genetic characterization of Charcot-Marie-Tooth disease.