T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy

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Ann Neurol. 2006 Jan 25;59(2):358-364

T118M PMP22 mutation causes partial loss of function and HNPP-like

neuropathy.

Shy ME, Scavina MT, A, Krajewski KM, Li J, Kamholz J, Kolodny

E, Szigeti K, Fischer RA, Mustafa Saifi G, Scherer SS, Lupski JR.

Department of Neurology and the Center for Molecular Medicine and

Genetics, Wayne State University, Detroit, MI.

OBJECTIVE: To determine the clinical consequences of the PMP22 point

mutation, T118M, which has been previously considered to either cause

an autosomal recessive form of Charcot-Marie-Tooth (CMT) disease or

be a benign polymorphism.

METHODS: We analyzed patients from five separate kindreds and

characterized their peripheral nerve function by clinical and

electrophysiological methods.

RESULTS: All heterozygous patients had clinical and/or

electrophysiological features of a neuropathy similar to hereditary

neuropathy with liability to pressure palsies (HNPPs). The homozygous

patient had a severe axonal neuropathy without features of

demyelination.

INTERPRETATION: These findings suggest that T118M PMP22 retains some

normal PMP22 activity, allowing the formation of compact myelin and

normal nerve conduction velocities in the homozygous state. Taken

together, these findings suggest that T118M is a pathogenic mutation

causing a dominantly inherited form of CMT by a partial loss of PMP22

function.