Variable phenotypes are associated with PMP22 missense mutations.

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Neuromuscul Disord. 2010 Dec 29.

Variable phenotypes are associated with PMP22 missense mutations.

Russo M, Laurá M, Polke JM, MB, Blake J, Brandner S, RA, Houlden H,

DL, Lunn MP, Reilly MM.

MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences,

UCL Institute of Neurology, London, UK; Department of Neurosciences, Psychiatry

and Anaesthesiology, University of Messina, Italy.

Abstract

Charcot-Marie-Tooth disease (CMT) is the commonest hereditary neuropathy

encompassing a large group of clinically and genetically heterogeneous

disorders. The commonest form of CMT, CMT1A, is usually caused by a 1.4 megabase

duplication of chromosome 17 containing the PMP22 gene. Mutations of PMP22 are a

less common cause of CMT. We describe clinical, electrophysiological and

molecular findings of 10 patients carrying PMP22 missense mutations.

The phenotype varied from mild hereditary neuropathy with liability to pressure

palsies (HNPP) to severe CMT1. We identified six different point mutations,

including two novel mutations. Three families were also found to harbour a

Thr118Met mutation. Although PMP22 point mutations are not common, our findings

highlight the importance of sequencing the PMP22 gene in patients with variable

CMT phenotypes and also confirm that the PMP22 Thr118Met mutation is associated

with a neuropathy albeit with reduced penetrance.