Mutational screening of the SH3TC2 gene in Greek patients with suspected demyelinating recessive Charcot-Marie-Tooth disease reveals a varied and unusual phenotypic spectrum

J Peripher Nerv Syst. 2019 Mar;24(1):125-130. doi: 10.1111/jns.12305. Epub 2019 Feb 6.


Charcot-Marie-Tooth disease type 4 C (CMT4C) is an autosomal recessive form of demyelinating peripheral neuropathy caused by mutations in SH3TC2, characterized by early onset, spine deformities, and cranial nerve involvement. We screened SH3TC2 in 50 unrelated Greek patients with suspected demyelinating Charcot-Marie-Tooth disease and pedigree compatible with recessive inheritance. All patients had been previously screened for PMP22, GJB1, and MPZ mutations. We found five previously identified pathogenic mutations in SH3TC2 distributed among 13 patients in homozygosity or compound heterozygosity (p. Arg954Stop, Arg1109Stop, Gln892Stop, Ala878Asp, and Arg648Trp). Although most cases had early onset and spine deformities were almost omnipresent, a wide phenotypic spectrum was observed. Particularly notable were two siblings with Roussy-Lévy syndrome and one patient with young-onset trigeminal neuralgia. In conclusion, mutations in SH3TC2 are responsible for 26% of Greek patients with suspected CMT4, identifying CMT4C as the most common recessive demyelinating neuropathy in the Greek population, in accordance with other Mediterranean cohorts.

Keywords: CMT; CMT4C; Charcot-Marie-tooth; Roussy-Lévy syndrome; SH3TC2.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Charcot-Marie-Tooth Disease* / genetics
  • Charcot-Marie-Tooth Disease* / pathology
  • Charcot-Marie-Tooth Disease* / physiopathology
  • Child
  • Codon, Nonsense
  • Female
  • Greece
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Mutation, Missense
  • Phenotype


  • Codon, Nonsense
  • Intracellular Signaling Peptides and Proteins
  • SH3TC2 protein, human

Supplementary concepts

  • Charcot-Marie-Tooth disease, Type 4C