Mosaicism for a pathogenic MFN2 mutation causes minimal clinical features of CMT2A in the parent of a severely affected child

Neurogenetics. 2017 Jan;18(1):49-55. doi: 10.1007/s10048-016-0504-2. Epub 2017 Jan 6.


Charcot-Marie-Tooth disease (CMT) refers to a genetically heterogeneous group of disorders which cause a peripheral motor and sensory neuropathy. The overall prevalence is 1 in 2500 individuals. Mutations in the MFN2 gene are the commonest cause for the axonal (CMT2) type. We describe a Caucasian 5-year old girl affected by CMT2A since the age of 2 years. She presented with unsteady gait, in-turning of the feet and progressive foot deformities. Nerve conduction studies suggested an axonal neuropathy and molecular testing identified a previously reported pathogenic variant c.1090C > T, p.(Arg364Trp) in the MFN2 gene. This variant was also detected in a mosaic state in blood and saliva by Sanger sequencing in her subjectively healthy father. Next generation sequencing showed that the level of mosaicism was 21% in blood and 24% in saliva. A high recurrence risk was given because the father had proven somatic mosaicism and an affected child implying gonadal mosaicism. The parents were referred for pre-implantation genetic diagnosis. To the best of our knowledge, this is the first reported case of somatic mosaicism for MFN2. This study has important implications for genetic counselling in families with CMT2A.

Keywords: CMT2A; Charcot-Marie-tooth disease; MFN2; Mosaicism.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology*
  • Child, Preschool
  • Father-Child Relations
  • Female
  • GTP Phosphohydrolases / genetics*
  • Humans
  • Male
  • Mitochondrial Proteins / genetics*
  • Mosaicism*
  • Mutation, Missense*
  • Nuclear Family
  • Parents
  • Pedigree
  • Phenotype
  • Severity of Illness Index


  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • MFN2 protein, human