Characterization of a Portuguese family with Charcot-Marie-Tooth disease type 1E due to a novel point mutation in the PMP22 gene.

Introduction: Point mutations in the Peripheral Myelin Protein 22 (PMP22) gene comprise less than 5% of the Charcot-Marie-Tooth (CMT) type 1 cases, and individualize either the CMT 1E subtype, or Hereditary Neuropathy with Liability to Pressure Palsy. The phenotype of CMT 1E presents with a severe early-onset polyneuropathy associated with deafness, although the clinical spectrum is broad.

Case Report: We describe a novel PMP22 gene point mutation (c.84G>T;p.(Trp28Cys)) in three patients of a Portuguese family with variable phenotypes, ranging from asymptomatic to mild complaints of distal limb numbness and gait difficulties, with the age of onset of symptoms ranging from mid-twenties to late-sixties, and no associated disability. In all affected patients, there was evidence of diffuse demyelinating sensorimotor polyneuropathy. Hearing loss does not seem to be associated with this variant, albeit neuropathic pain was reported.

Conclusions: These findings suggest that this particular point mutation in the PMP22 gene is associated with a mild phenotype, further emphasizing that there are still unknown mechanisms (genetic and/or epigenetic) that may play a role in the clinical spectrum of CMT1E patients. Next generation sequencing panels including commonly mutated genes in CMT should be considered in CMT1 cases negative for PMP22 gene duplication.