PMP22

About PMP22

PMP22 Peripheral Myelin Protein 22 on chromosome 17p12 encodes a small membrane glycoprotein that is a component of compact myelin in the peripheral nervous system, made by Schwann cells. The most common mutation is a duplication of a 1.4 megabase region containing PMP22, arising through unequal crossing over between flanking repeats, which causes Charcot Marie Tooth disease type 1A, the most common form of the most common inherited neuropathy. Charcot Marie Tooth disease as a whole affects roughly 1 in 2,500 people. CMT1A causes slowly progressive distal muscle weakness and wasting, reduced reflexes, foot deformities such as high arches and hammer toes, and sensory loss, typically beginning in the first two decades of life. Nerve conduction velocities are uniformly and markedly slowed, reflecting demyelination. The reciprocal deletion of the same region causes hereditary neuropathy with liability to pressure palsies, in which episodes of focal numbness and weakness follow minor compression of nerves. Point mutations in PMP22 cause more severe neuropathies such as Dejerine Sottas syndrome. The disease is named after Jean Martin Charcot, Pierre Marie, and Howard Henry Tooth, who described it in 1886. There is no disease modifying treatment, so care relies on physical therapy, orthotics, and surgery, and PMP22 lowering approaches are being studied.