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.