Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease.

Abstract

Recently, mutations affecting different domains of dynamin-2 (DNM2) were associated alternatively with autosomal dominant centronuclear myopathy or dominant intermediate (demyelinating and axonal) Charcot-Marie-Tooth disease (CMT) type B. To assess the etiologic role of DNM2 in CMT. We performed a mutational screening of DNM2 exons 13 through 16 encoding the pleckstrin homology domain in a large series of CMT patients with a broad range of nerve conduction velocities and without mutations in more common genes. We identified two novel DNM2 mutations that cosegregated with purely axonal CMT in two pedigrees without clinical evidence of primary myopathy. Patients with axonal Charcot-Marie-Tooth disease type 2 neuropathy without mutations in more common genes should undergo investigation for DNM2 pleckstrin homology.