Novel GJB1 mutation causing adult-onset Charcot–Marie–Tooth disease in a female patient

Abstract Charcot–Marie–Tooth disease (CMT), which is the eponym for hereditary motor and sensory neuropathy (HMSN), affects ∼1 in 2500 individuals. The most common subtype of X-linked CMT, CMTX1, is caused by mutations in GJB1 , the gene encoding connexin 32, a gap junction protein in myelinated Schwann cells. We report a woman, who presented at the age of 56 years with gait unsteadiness and tingling in her feet. Clinical investigation revealed impaired sensation to pinprick, light touch and vibration in her distal lower limbs. Ankle reflexes were bilaterally absent. Sequencing revealed a novel heterozygous c.712C>T (p.R238C) mutation in the GJB1 gene. This mutation is predicted to result in the loss of disulfide bonds and thus in abnormal protein structure. In this woman, the reported novel GJB1 mutation resulted in sensory abnormalities, slowly progressive loss of distal lower limb strength, and notable loss of balance, with onset of symptoms late in adult age.