Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease

BMC Med Genet. 2020 Mar 2;21(1):45. doi: 10.1186/s12881-020-0984-7.


Background: Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neurological disorders. A growing number of genes, involved in glial and neuronal functions, have been associated with different subtypes of CMT leading to improved diagnostics and understanding of pathophysiological mechanisms. However, some patients and families remain genetically unsolved.

Methods: We report on a German family including four affected members over three generations with a CMT phenotype accompanied by cognitive deficits, predominantly with regard to visual abilities and episodic memory.

Results: A comprehensive clinical characterization followed by a sequential diagnostic approach disclosed a heterozygous rare SEPT9 missense variant c.1406 T > C, p.(Val469Ala), that segregates with disease. SEPT9 has been linked to various intracellular functions, such as cytokinesis and membrane trafficking. Interestingly, SEPT9-mutations are known to cause hereditary neuralgic amyotrophy (HNA), a recurrent focal peripheral neuropathy.

Conclusion: We, for the first time, present a SEPT9 variant associated to a CMT phenotype and suggest SEPT9 as new sufficient candidate gene in CMT.

Keywords: Charcot-Marie-Tooth; Inherited neuropathy; Next generation sequencing; SEPT9; Septin.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine / genetics
  • Amino Acid Substitution / genetics
  • Charcot-Marie-Tooth Disease / diagnosis
  • Charcot-Marie-Tooth Disease / genetics*
  • Family
  • Female
  • Gene Frequency
  • Genes, Dominant
  • Germany
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation, Missense
  • Pedigree
  • Polymorphism, Single Nucleotide*
  • Septins / genetics*
  • Valine / genetics
  • Young Adult


  • SEPTIN9 protein, human
  • Septins
  • Valine
  • Alanine