Molecular characterization of Turkish patients with demyelinating Charcot-Marie-Tooth disease.


Karakaya T., Turkyilmaz A., Sager G., Inan R., Yarali O., Cebi A. H., ...More

Neurogenetics, vol.23, no.3, pp.213-221, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 23 Issue: 3
  • Publication Date: 2022
  • Doi Number: 10.1007/s10048-022-00693-6
  • Journal Name: Neurogenetics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, EMBASE, MEDLINE
  • Page Numbers: pp.213-221
  • Keywords: Demyelinating Charcot-Marie-Tooth disease, GJB1, NEFL, PMP22, SBF2, GENETIC SUBTYPES, MUTATIONAL ANALYSIS, NEUROPATHY, FREQUENCY, SPECTRUM, PSEUDOPHOSPHATASE, GUIDELINES, VARIANTS, FAMILIES, MTMR13
  • Karadeniz Technical University Affiliated: Yes

Abstract

Charcot-Marie-Tooth (CMT) disease represents a distinct subgroup of inherited peripheral neuropathies with a significant prevalence throughout the world and manifests both phenotypic and genetic heterogeneity. Electrophysiological studies subclassify CMT mainly as demyelinating or axonal types. In this study, we investigated the molecular characteristics of a Turkish cohort of 23 probands out of 34 symptomatic demyelinating CMT individuals from January 2019 to December 2021. In order to identify the underlying genetic cause, we applied a rational algorithm: PMP22 gene was initially analyzed for duplication, if PMP22-duplication testing was negative, other most causative genes (GJB1, MPZ) and PMP22 were then sequenced and if no variant was detected at aforementioned tests, whole exome sequencing (WES) test was finally performed. A total of 17 patients (congruent to 74%; n= 23) were found to harbor a disease-causing variant in demyelinating CMT-related genes and among the variants, PMP22-duplication was the most frequent (congruent to 41%). CMT1, CMTX, and CMT4 subtypes were manifested in ten, five, and two individuals respectively. GJB1 and SBF2 genes were the only detected genes associated with the CMTs other than CMT1. We also reported totally five novel variants: c.379A > C (p.Ile127Leu) and c.548G > T (p.Arg183Leu) variants in GJB1, c.988G > T (p.Glu330Ter) variant in NEFL, c.765_770delCCCTAT (p.Pro256 _Ile257del) and c.2552A > C (p.His851Pro) variants in SBF2. As the understanding of pathophysiology and molecular mechanisms of CMT continues to evolve rapidly, many therapeutic strategy options including promising small-molecular compounds, gene replacement therapy, or disease-modifying therapies will soon be implemented in the clinical setting.