A novel MFN2 mutation causes variable clinical severity in a multi-generational CMT2 family

Neuromuscul Disord. 2019 Feb;29(2):134-137. doi: 10.1016/j.nmd.2018.12.008. Epub 2018 Dec 21.


Dominant mutations in MFN2 cause a range of phenotypes, including severe, early-onset axonal neuropathy, "classical CMT2", and late-onset axonal neuropathy. We found a novel MFN2 mutation - c.283A>G (p.Arg95Gly) - that results in an axonal neuropathy with variable clinical severity in a multigenerational family. In affected family members, electromyography showed moderate to severe, chronic denervation in distal muscles. Such variable clinical severity highlights the need to do careful assessments of at risk individuals when assessing MFN2 variants.

Keywords: CMT2A; Charcot-Marie-Tooth disease Type 2; Late-onset axonal neuropathy; Multigenerational affection; Variable penetrance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged, 80 and over
  • Charcot-Marie-Tooth Disease / diagnosis*
  • Charcot-Marie-Tooth Disease / genetics
  • Female
  • GTP Phosphohydrolases / genetics*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Mutation*
  • Pedigree
  • Phenotype
  • Severity of Illness Index
  • Young Adult


  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • MFN2 protein, human

Supplementary concepts

  • Charcot-Marie-Tooth disease, Type 2A