Although named over 100 years ago, identification of subtypes of Charcot-Marie-Tooth has rapidly expanded in the preceding decades with the advancement of genetic sequencing, including type 2F (CMT2F), due to mutations in heat shock protein 27 (Hsp27).
Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie Tooth Disease.
However, we present a family with a novel mutation in the C-terminus of HSP27 (p.Gln175X) [corrected] with a motor predominant distal neuropathy but with definite sensory involvement compatible with CMT2.
Twenty-one members of a five generation Sardinian family have been studied, including thirteen members affected by peroneal muscular atrophy and proved heterozygous for the known HSP27R127W mutation.
Recently, mutations in both the small heat shock protein 27 (HSP27 or HSPB1) and 22 (HSP22 or HSPB8) genes have been reported to cause autosomal dominant CMT with minimal sensory involvement (CMT 2F/CMT2L) and autosomal dominant distal hereditary motor neuropathy type II (dHMN II).
The frequency of the Hsp27 mutation is 0.9% (1/111) in Chinese patients with CMT disease in our study, and the phenotypes were characterized by later onset (age, 35-60 years) and mild sensory impairments.