Genetic Study of Demyelinating form of Autosomal-Recessive Charcot–Marie–Tooth Diseases in a Turkish Family

Abstract

Charcot–Marie–Tooth (CMT) disease is a clinically and genetically heterogeneous group of inherited peripheral motor and sensory neuropathies characterized by distal muscle weakness atrophy predominantly in the lower extremities, diminished or absent deep tendon reflexes, distal sensory loss and skeletal deformities. Mode of inheritance could be either autosomal dominant, autosomal recessive, or X-linked. The autosomal-recessive subgroup of CMT (AR-CMT) neuropathies is heterogeneous as well. To date, nine demyelinating loci have been implicated in CMT4 and seven genes have been identified. It has been screened in this study for the presence of mutations in the coding region of GDAP1 and genetic linkage analyses of CMT4B1, CMT4B2, CMT4C, CMT4D, CMT4E, and CMT4F loci were tested in a Turkish family presenting recessively inherited form of CMT disease characterized by severe motor weakness. We did not find any mutations in GDAP1 and genetic linkage excluded for the six demyelinating genes loci (CMT4B1, CMT4B2, CMT4C, CMT4D, CMT4E, and CMT4F). Our findings indicate that another locus may be associated with AR-CMT disease.

Keywords:

• Charcot-Marie-Tooth disease
• autosomal recessive
• demyelinating
• genetic
• linkage analysis