The Importance of Multiple Gene Analysis for Diagnosis and Differential Diagnosis in Charcot Marie Tooth Disease

Turk Neurosurg. 2021;31(6):888-895. doi: 10.5137/1019-5149.JTN.33661-21.3.

Abstract

Aim: To investigate the genetic etiology of Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy (HMSN).

Material and methods: We herein examined 55 non-related patients with a suspicion of CMT phenotype or HMSN using a customized multigene panel based on the next-generation sequencing technique. All cases were previously analyzed for PMP22 duplication with the Multiplex Ligand Probe Amplification (MLPA) method.

Results: In 13 cases (7.15%), we identified a pathogenic/likely pathogenic variant. The affected genes were MARS1, NDRG1, GJB1, GDAP1, MFN2, PRX, SH3TC2, and FGD4. In six cases (10.9%), novel variants were identified: pathogenic variants in GJB1 and FGD4 genes, variants of unknown significance (VUS) in HSPB3, CHRNA1, ARHGEF10, and KIF5A genes. In 21 cases (11.55%), VUS with the genes HSPB3, KIF1B, SCN11A, CHRNA1, HSPB1, FIG4, ARHGEF10, DHTKD1, SBF1, EGR2, SBF2, IGHMBP2, KIF5A, and DNAJB2 were identified.

Conclusion: In this study, we had a 7.15% diagnosis rate with the NGS (Next Generation Sequencing) method in the CMT disease. Targeted next-generation sequencing panels are beneficial, time-saving, and cost-effective in the diagnosis of CMT.

MeSH terms

  • Charcot-Marie-Tooth Disease* / diagnosis
  • Charcot-Marie-Tooth Disease* / genetics
  • DNA-Binding Proteins
  • Diagnosis, Differential
  • Flavoproteins
  • HSP40 Heat-Shock Proteins
  • Heat-Shock Proteins
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Ketoglutarate Dehydrogenase Complex
  • Kinesins
  • Microfilament Proteins
  • Molecular Chaperones
  • Phosphoric Monoester Hydrolases
  • Transcription Factors

Substances

  • DNA-Binding Proteins
  • DNAJB2 protein, human
  • FGD4 protein, human
  • Flavoproteins
  • HSP40 Heat-Shock Proteins
  • HSPB3 protein, human
  • Heat-Shock Proteins
  • IGHMBP2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • KIF5A protein, human
  • Microfilament Proteins
  • Molecular Chaperones
  • SBF1 protein, human
  • Transcription Factors
  • DHTKD1 protein, human
  • Ketoglutarate Dehydrogenase Complex
  • FIG4 protein, human
  • Phosphoric Monoester Hydrolases
  • Kinesins