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 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 31
  • Publication Date: 2021
  • Doi Number: 10.5137/1019-5149.jtn.33661-21.3
  • Journal Name: Turkish Neurosurgery
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
  • Page Numbers: pp.888-895
  • Keywords: Charcot-marie-tooth, Next generation sequencing, Multigene testing, Hereditary neuropathy, DISTAL SYMMETRIC POLYNEUROPATHY, NEUROPATHIES, ASSOCIATION, MPZ
  • Bursa Uludag University Affiliated: Yes

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.