De Novo
MFN2
p.
Arg95Met
in Severe Charcot‐Marie‐Tooth Disease Type
2A
Hsi‐Yen Lee, Wen‐Ling Cheng, Shin‐Hung Pan, Chia‐Ju Lee, Yau‐Huei Wei, Chin‐San Liu ABSTRACT
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.