Frontiers in Genetics (Jun 2024)

Genetic Landscape of SH3TC2 variants in Russian patients with Charcot–Marie–Tooth disease

  • Olga Shchagina,
  • Aysylu Murtazina,
  • Polina Chausova,
  • Mariya Orlova,
  • Elena Dadali,
  • Sergei Kurbatov,
  • Sergei Kurbatov,
  • Sergey Kutsev,
  • Aleksander Polyakov

DOI
https://doi.org/10.3389/fgene.2024.1381915
Journal volume & issue
Vol. 15

Abstract

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Introduction:Charcot–Marie–Tooth disease type 4C (CMT4C) OMIM#601596 stands out as one of the most prevalent forms of recessive motor sensory neuropathy worldwide. This disorder results from biallelic pathogenic variants in the SH3TC2 gene.Methods:Within a cohort comprising 700 unrelated Russian patients diagnosed with Charcot–Marie–Tooth disease, we conducted a gene panel analysis encompassing 21 genes associated with hereditary neuropathies. Among the cohort, 394 individuals exhibited demyelinating motor and sensory neuropathy.Results and discussion:Notably, 10 cases of CMT4C were identified within this cohort. The prevalence of CMT4C among Russian demyelinating CMT patients lacking the PMP22 duplication is estimated at 2.5%, significantly differing from observations in European populations. In total, 4 novel and 9 previously reported variants in the SH3TC2 gene were identified. No accumulation of a major variant was detected. Three previously reported variants, c.2860C>T p. (Arg954*), p. (Arg658Cys) and c.279G>A p. (Lys93Lys), recurrently detected in unrelated families. Nucleotide alteration p. (Arg954*) is present in most of our patients (30%).

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