Etiological Role of Dynamin in Charcot-Marie-Tooth Disease

Charcot–Marie–Tooth disease (CMT) is one of the most common inherited neuropathy, with estimated prevalence of 17 to 40 in 100,000 affected (Patzkó, & Shy, 2011). CMT is characterized by atrophy of muscle tissue and loss of touch sensation of limb, predominantly in the feet and legs, foot drop, and hammer toes. The most frequent initial symptoms include foot drop, claw toe, and muscle wasting in the hands. Symptoms in the advanced cases may include muscle waste in the hands and fore arms, neck and shoulder, vocal cords, which leads to scoliosis and malfunction in chewing, swallowing, or speaking. The defective neurotransmission stems from either degradation of myelin sheath or breakdown of neuronal axon, which define primary forms of this disease, CMT type 1 and CMT type 2 respectively. CMT type 1 and CMT type 2 can be clinically distinguished based on nerve conduction velocity (NCV). Slow NCV (less than 38 m/s) is characteristic of demyelinating CMT type 1, and the average NCV is slightly below normal, but above 38 m/s in CMT type 2. In addition, dominant intermediate subtypes of CMT (DI-CMT) have been identified, which are characterized by NCVs overlapping both demyelinating and axonal range (25 45 m/s). Number of genes and gene loci has been involved in the pathogenesis of CMT, and despite of diversity of the responsible genes, they are involved in common molecular pathways within Schwann cells and axons that cause these genetic neuropathies (Patzkó & Shy, 2011). CMT Type 1 primarily affects the myelin sheath, and is inherited as dominant, recessive or X-linked. Type 2 primarily affects the axon, and is either dominant or recessive. DI-CMT is classified type A (DI-CMTA), type B (DI-CMTB) type C (DI-CMTC), and type D (DI-CMTD) according to responsible genes and gene loci. In this review, we focus on dynamin 2 and the mutations, which are responsible for DICMTB and axonal CMT type 2. We explain physiological role of dynamin 2 in the regulation of microtubules and propose possible pathogenesis of CMT attributed to dynamin 2 mutants.