A novel p.Gln175X [corrected] premature stop mutation in the C-terminal end of HSP27 is a cause of CMT2.
Mutations in the gene HSPB1, encoding the small heat shock protein 27 (HSP27), are a cause of distal hereditary motor neuropathy (dHMN) and axonal Charcot-Marie-Tooth disease (CMT2). dHMN and CMT2 are differentiated by the presence of a sensory neuropathy in the latter although in the case of HSPB1 this division is artificial as CMT2 secondary to HSPB1 mutations is predominantly a motor neuropathy with only minimal sensory involvement. A recent study in mice has suggested that mutations in the C-terminus result in a motor only phenotype resembling dHMN, whereas mutations at the N-terminus result in a CMT2-like phenotype. 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. This case highlights the artificial distinction between patients with motor predominant forms of CMT2 and dHMN and argues against the hypothesis that mutations in the C-terminus have no sensory involvement.
MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UK.
Alexander M
AM
Rossor
Gabrielle L
GL
Davidson
Julian
J
Blake
James M
JM
Polke
Sinéad M
SM
Murphy
Henry
H
Houlden
Amy
A
Innes
Bernadett
B
Kalmar
Linda
L
Greensmith
Mary M
MM
Reilly
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020836:Protein Structure, Quaternary
D018389:Codon, Nonsense; D055551:HSP27 Heat-Shock Proteins