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Neurogenetics

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13.05.2022 | Original Article

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

verfasst von: Taner Karakaya, Ayberk Turkyilmaz, Gunes Sager, Rahsan Inan, Oguzhan Yarali, Alper Han Cebi, Yasemin Akin

Erschienen in: Neurogenetics | Ausgabe 3/2022

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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 (≅ 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 (≅ 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.

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Titel: Molecular characterization of Turkish patients with demyelinating Charcot-Marie-Tooth disease
verfasst von: Taner Karakaya
Ayberk Turkyilmaz
Gunes Sager
Rahsan Inan
Oguzhan Yarali
Alper Han Cebi
Yasemin Akin
Publikationsdatum: 13.05.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: Neurogenetics / Ausgabe 3/2022
Print ISSN: 1364-6745
Elektronische ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-022-00693-6

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