A novel missense mutation of the PMP22 gene causing HNPP without generalized electrophysiologic abnormalities

The peripheral myelin protein 22 (PMP22) is abundantly expressed by Schwann cells of peripheral nerves and plays a major role in the formation and maintenance of compact myelin. Mutations in the PMP22 gene on chromosome 17p11.2 account for Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP). Both syndromes follow an autosomal dominant inheritance. A duplication of the PMP22 gene leads to CMT1A while deletion of the same gene fragment causes HNPP. HNPP is characterized by the recurrence of transient nerve palsies which may be caused even by minor pressure trauma to the peripheral nerves. Electrophysiologically, nerve conduction blocks in clinically unaffected nerves are used as diagnostic criteria for HNPP. Up to now, 10 point mutations in the PMP22 gene have been described which are also associated with a HNPP phenotype. In all patients described, clinically manifest nerve palsies were accompanied by electrophysiological signs of a generalized neuropathy. We describe a novel missense mutation of the PMP22 gene causing a phenotype lacking electrophysiological abnormalities in clinically unaffected nerves.