The importance of multiple gene analysis for diagnosis and differential diagnosis in charcot marie tooth disease


YALÇINTEPE S., GÜRKAN H., DEMİR S., ÖZEMRİ SAĞ Ş. , ATLI E. İ. , ATLI E., ...More

Turkish Neurosurgery, vol.31, pp.888-895, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 31
  • Publication Date: 2021
  • Doi Number: 10.5137/1019-5149.jtn.33661-21.3
  • Title of Journal : Turkish Neurosurgery
  • Page Numbers: pp.888-895
  • Keywords: Charcot-marie-tooth, Next generation sequencing, Multigene testing, Hereditary neuropathy, DISTAL SYMMETRIC POLYNEUROPATHY, NEUROPATHIES, ASSOCIATION, MPZ

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.