Molecular and clinical features of inherited neuropathies due to PMP22 duplication

•PMP22 is a transmembrane glycoprotein important in normal functioning of myelin.•PMP22 gene duplication leads to a toxic gain of function.•The gene–dose effect disrupts myelin stoichiometry and remodelling.•Further leading to conformational instability, cell death and dysfunctional myelin.•CMT1A caused by PMP22 duplication, manifests with mainly demyelinating neuropathy.

PMP22 is a transmembrane glycoprotein component of myelin, important for myelin functioning. Mutation of PMP22 gene which encodes for the production of PMP22 glycoprotein is associated with a variety of inherited neuropathies. This literature review sought to review the molecular mechanism and clinical features of inherited neuropathies caused by PMP22 duplication. PMP22 duplication causes CMT1A which accounts for more than half of all CMT cases and about 70% of CMT1 cases. It manifests with muscle weakness, depressed reflexes, impaired distal sensation, hand and foot deformities, slowing of NCV and onion bulbs. With no specific treatment available, it is managed conservatively. Future treatment may be based on the molecular genetics of the disease.