De Novo MFN2 p.Arg95Met in Severe Charcot-Marie-Tooth Disease Type 2A.

BACKGROUND AND AIMS: Mitofusin 2 (MFN2)-related Charcot-Marie-Tooth disease type 2A (CMT2A) is often associated with early onset, severe progressive weakness, distal wasting, and reduced motor and sensory response amplitudes.

CASE REPORT: We report a 30-year-old Taiwanese woman with infancy-onset, severe axonal sensorimotor neuropathy, progressive distal weakness and wasting, optic atrophy, bilateral sensorineural hearing loss, hypophonia, and wheelchair dependence from adolescence. Nerve conduction study was consistent with severe chronic axonal sensorimotor polyneuropathy. Whole-exome sequencing identified a heterozygous de novo Mitofusin 2 (MFN2) variant, NM_014874.4:c.284G>T, predicting p.Arg95Met.

INTERPRETATION: This case expands the genotypic spectrum of MFN2-related Charcot-Marie-Tooth disease type 2A and supports the clinical importance of the Arg94/Arg95 region in severe early-onset MFN2 neuropathy.