PMP22genen

PMP22, or peripheral myelin protein 22, is a gene that encodes a small four-pass transmembrane glycoprotein expressed by Schwann cells in the peripheral nervous system. The protein is a major component of compact peripheral myelin and is thought to contribute to myelin stability and the normal structure of the myelin sheath. The PMP22 gene is located on chromosome 17 in humans, within a region prone to copy number variation. The standard transcript yields a protein of about 22 kDa.

Genetic disorders caused by PMP22 dosage changes are among the best characterized hereditary neuropathies. A duplication of the region containing PMP22 leads to increased gene dosage and causes Charcot–Marie–Tooth disease type 1A (CMT1A), the most common inherited neuropathy. Clinically, CMT1A presents with slowly progressive distal weakness, sensory loss, and foot deformities; it is typically inherited in an autosomal dominant manner. Conversely, a heterozygous deletion of the PMP22 region causes hereditary neuropathy with liability to pressure palsies (HNPP), characterized by episodic, focal neuropathies after minor compression or trauma; this condition is also autosomal dominant with variable penetrance.

Other rarer PMP22 variants, including intragenic point mutations, can produce demyelinating neuropathies with variable phenotypes but are much less common than the dosage-related disorders.

Diagnosis and management: Genetic testing is used to detect PMP22 copy number changes (e.g., MLPA or array CGH) and, when indicated, sequencing for point mutations. Management is supportive and may include physical therapy, occupational therapy, orthotics, and regular nerve conduction studies to monitor progression.