CMT 2F:Heat shock protein 27 R127W mutation:evidence of a continuum between

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J Neurol Neurosurg Psychiatry. 2010 Sep;81(9):958-62.

Heat shock protein 27 R127W mutation: evidence of a continuum between axonal

Charcot-Marie-Tooth and distal hereditary motor neuropathy.

Solla P, Vannelli A, Bolino A, Marrosu G, Coviello S, Murru MR, Tranquilli S,

Corongiu D, Benedetti S, Marrosu MG.

Centro Sclerosi Multipla, Ospedale Binaghi, University of Cagliari, Cagliari,

Italy.

Abstract

BACKGROUND: Heat shock protein 27 (HSP27) mutations have been reported to cause

both Charcot-Marie-Tooth disease (CMT) type 2F and distal hereditary motor

neuropathy (dHMN) although never previously in a single family.

OBJECTIVE: To analyse clinical and electrophysiological findings obtained in a

single large Sardinian family bearing the HSP27 R127W mutation.

METHODS: 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 HSP27 R127W mutation. Twelve patients and

eight unaffected relatives were subjected to clinical examination. A

standardised electrophysiological study was performed in eleven patients and six

unaffected relatives.

RESULTS: Mean age at onset (+/-SD) was 31.2+/-7.2 years. Mean age at

investigation was 45.2+/-12.9 years and mean disease duration at the time of

investigation was 14+/-12.9 years. According to current criteria for CMT2 and

dHMN, of the 10 patients who had undergone both clinical and neurophysiological

examination, five were diagnosed as CMT2, two as dHMN and a further two patients

were labelled as an intermediate type. Finally, due to the presence of spastic

paraplegia, the index patient did not meet established criteria for the

diagnosis of CMT or dHMN.

DISCUSSION: Findings obtained in the present study, broadening the spectrum of

clinical manifestations of disorders associated with HSP27 mutations, support

the hypothesis of a continuum between CMT2 and dHMN forms and suggest a possible

common spectrum between these entities and several forms of CMT plus pyramidal

features (HMSN V), providing important implications for molecular genetic

testing.