Rare Variants of Putative Candidate Genes Associated With Sporadic Meniere's Disease in East Asian Population.

摘要: Objectives: The cause of Meniere's disease (MD) is unclear but likely involves genetic and environmental factors. aim this study was to investigate the basis underlying MD by screening putative candidate genes for MD. Methods: Sixty-eight patients who met diagnostic criteria Barany Society were included. We performed targeted gene sequencing using next generation (NGS) panel composed 45 MD-associated genes. identified rare variants causing non-synonymous amino acid changes, stop codons, insertions/deletions in coding regions, excluded common with minor allele frequency >0.01 public databases. pathogenicity analyzed various predictive tools protein structural modeling. Results: average read depth regions 1446.3-fold, 99.4% covered 20 or more reads, achieving high quality sequencing. After variant filtering, annotation, interpretation, we a total 15 heterozygous 12 (17.6%) sporadic patients. Among them, four detected familial (DTNA, FAM136A, DPT), remaining 11 (PTPN22, NFKB1, CXCL10, TLR2, MTHFR, SLC44A2, NOS3, NOTCH2). Three had two All not our healthy controls (n = 100). No significant differences observed between without terms sex, mean age onset, bilaterality, type MD, hearing threshold at diagnosis. Conclusions: Our some related formation inner ear structures, immune-associated process, systemic hemostasis derangement, suggesting multiple predispositions development