Genetic dosage compensation via co-occurrence of <i>PMP22</i> duplication and <i>PMP22</i> deletion

Abstract

Charcot-Marie-Tooth disease type 1 A (CMT1A, OMIM #118220) and hereditary neuropathy with liability to pressure palsies (HNPP or tomaculous neuropathy, OMIM #162500) are autosomal dominantly inherited neuropathies caused by genomic rearrangements on chromosome 17p11.2-p12 containing PMP22 . Heterozygous PMP22 duplications result in a peripheral neuropathy characterized by distal muscular atrophy, foot deformities, sensory deficits, and generally reduced nerve conduction velocities in the demyelinating range (CMT1A). In contrast, a heterozygous PMP22 deletion results in HNPP that is characterized by recurrent transient episodes of transient focal compressive neuropathies manifesting as weakness, sensory loss, or both, with electrophysiology showing multifocal slowing at the sites of compression.