AUTHOR=Zou Jing , Zhang Guoping , Li Hongbin , Zhao Zikai , Zhang Qing , Pyykkö Ilmari , Mäkitie Antti 

TITLE=Multiple genetic variants involved in both autoimmunity and autoinflammation detected in Chinese patients with sporadic Meniere's disease: a preliminary study

JOURNAL=Frontiers in Neurology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1159658

DOI=10.3389/fneur.2023.1159658

ISSN=1664-2295

ABSTRACT=Background: The mechanisms of Meniere’s disease (MD) remain largely unknown. The purpose of this study was to identify possible genetic variants associated with immune regulation in MD.
Methods: The whole immune genome of 16 Chinese patients diagnosed with sporadic MD was sequenced using next-generation sequencing. The in-house Chinese reference population data of MyGenostics Inc. that was archived from 2273 normal individuals was used as normal control. MRI was performed 24 h after intratympanic injection of gadolinium to detect endolymphatic hydrops.
Results: Definite pathological variants of MEFV (c.1223G>A, c.1105C>T), COL7A1 (c.5287C>T), and ADA (c.445C>T) contributing to the clinical phenotype were found in 3 patients. Limited and likely pathological variants of TLR3 (c.2228G>A) and RAB27A (c.560G>A) were detected in 1 patient each. The following definite pathological variants impairing the structure and function of translated proteins were detected in 10 patients, and multigene variants occurred in 5 patients: PRF1 (c.710C>A), UNC13D (c.1228A>C), COLEC11 (c.169C>T), RAG2 (c.200G>C), BLM (c.1937G>T), RNF31 (c.2533G>A), FAT4 (c.11498A>G), PEPD (c.788A>G), TNFSF12 (c.470G>A), VPS13B (c.11972A>T), TNFRSF13B (c.226G>A), ERCC6L2 (c.4613A>G), TLR3 (c.2228G>A), ADA (c.445C>T), PEPD (c.151G>A), and MOGS (c.2470G>A). The following limited pathological variants impairing the structure and function of translated proteins were detected in 5 patients, with double gene variants identified in 1 patient: EXTL3 (c.1396G>A), MTHFD1 (c.2057G>A), FANCA (c.2039T>C), LPIN2 (c.1814C>T), NBAS (c.4049T>C), and FCN3 (c.734G>A). 
Conclusion: Patients with sporadic MD carry multiple genetic variants involved in multiple steps of immune regulation, which might render patients susceptible to developing inflammation via both autoimmune and autoinflammation mechanisms upon stress.