Genotype-phenotype correlation in family with late onset CMT & an MPZ lys236del mutation

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J Neurol Neurosurg Psychiatry. 2005 Mar;76(3):442-4.

Genotype-phenotype correlation in a family with late onset CMT and an MPZ

lys236del mutation.

Sowden JE, Logigian EL, Malik K, Herrmann DN.

MB, BCh, Department of Neurology, Box 673, University of Rochester Medical

Center, 601 Elmwood Ave, Rochester, NY 14642, USA.

An in frame, lys236 deletion in the intracytoplasmic domain of myelin protein

zero (MPZ) has recently been designated as a mutation possibly associated with

Charcot-Marie-Tooth disease (CMT) but requiring further documentation.

In this report we present a detailed clinical, electrophysiological, and

genotype correlation in three generations of a family with the MPZ lys236del

mutation and provide further evidence that this mutation is associated with CMT.

The MPZ lys236del mutation is associated with an autosomal dominant, adult onset

CMT phenotype, with variable penetrance ranging from an asymptomatic state to

foot deformities, pedal numbness, and muscle cramps.

Nerve conduction studies disclose intermediate range, somewhat non-uniform

slowing of motor nerve conduction, which is accentuated in forelimb rather than

distal nerve segments.

Based on the contrasting finding of entirely normal conduction velocities (CV)

in a genetically affected 15 year old in this family, it remains to be

established whether CV slowing with this mutation is progressive in life, a

pattern that would contrast with CMT1a (PMP22 gene duplication).