PMP22
Peripheral Myelin Protein 22
Gene Summary
RefSeq / NCBIThis gene encodes an integral membrane protein that is a major component of myelin in the peripheral nervous system. Studies suggest two alternately used promoters drive tissue-specific expression. Various mutations of this gene are causes of Charcot-Marie-Tooth disease Type IA, Dejerine-Sottas syndrome, and hereditary neuropathy with liability to pressure palsies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Clinical Phenotype
Charcot-Marie-Tooth disease type 1A (CMT1A) — the most common inherited peripheral neuropathy. Slowly progressive distal weakness and sensory loss, pes cavus, hammer toes, and areflexia. Onset in first or second decade.
Molecular Mechanism
Duplication of the 1.5 Mb region at 17p12 containing PMP22 causes CMT1A (dosage sensitivity). Point mutations or deletion (1 copy) cause hereditary neuropathy with liability to pressure palsies (HNPP). PMP22 is a structural component of compact myelin.
Clinical Hallmarks & Key Evidence
CMT1A (PMP22 duplication) is the most common inherited neuropathy, with a prevalence of ~1 in 2,500. NCS shows uniform slowing of conduction velocity (<38 m/s in median nerve).
Skre H. Clin Genet. 1974;6(2):98-118.
Pes cavus (high arched foot) and hammer toes result from intrinsic foot muscle wasting and are present in >70% of CMT1A patients.
Pareyson D et al. Lancet Neurol. 2009;8(7):654-67.
Vincristine is contraindicated in CMT patients; it can precipitate severe acute neuropathy due to the underlying myelin vulnerability.
Graf WD et al. Ann Neurol. 1996;39(1):17-22.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.