Zou Jing, Zhang Guoping, Li Hongbin, Zhao Zikai, Zhang Qing, Pyykkö Ilmari, Mäkitie Antti
Department of Otolaryngology-Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Research Program in Systems Oncology, Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Front Neurol. 2023 May 18;14:1159658. doi: 10.3389/fneur.2023.1159658. eCollection 2023.
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.
The whole immune genome of 16 Chinese patients diagnosed with sporadic MD was sequenced using next-generation sequencing.
Definite pathological variants of (c.1223G>A, c.1105C>T), (c.5287C>T), and (c.445C>T) contributing to the clinical phenotype were found in three patients. Limited and likely pathological variants of (c.2228G>A) and (c.560G>A) were detected in one 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 five patients: (>), (c.1228A>C), (c.169C>T), (c.200G>C), (c.1937G>T), (c.2533G>A), (c.11498A>G), (c.788A>G), (c.470G>A), (c.11972A>T), (c.226G>A), (c.4613A>G), (c.2228G>A), (c.445C>T), (c.151G>A), and (c.2470G>A). The following limited pathological variants impairing the structure and function of translated proteins were detected in five patients, with double gene variants identified in one patient: (c.1396G>A), (c.2057G>A), (c.2039T>C), (c.1814C>T), (c.4049T>C), and (c.734G>A).
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 internal stress.
梅尼埃病（MD）的发病机制在很大程度上仍不清楚。本研究的目的是确定与MD免疫调节相关的可能基因变异。
使用下一代测序技术对16例诊断为散发性MD的中国患者的全免疫基因组进行测序。
在3例患者中发现了导致临床表型的明确病理变异（c.1223G>A、c.1105C>T）、（c.5287C>T）和（c.445C>T）。在1例患者中分别检测到有限且可能的病理变异（c.2228G>A）和（c.560G>A）。在10例患者中检测到以下影响翻译后蛋白质结构和功能的明确病理变异，5例患者出现多基因变异：（>）、（c.1228A>C）、（c.169C>T）、（c.200G>C）、（c.1937G>T）、（c.2533G>A）、（c.11498A>G）、（c.788A>G）、（c.470G>A）、（c.11972A>T）、（c.226G>A）、（c.4613A>G）、（c.2228G>A）、（c.445C>T）、（c.151G>A）和（c.2470G>A）。在5例患者中检测到以下影响翻译后蛋白质结构和功能的有限病理变异，1例患者鉴定出双基因变异：（c.1396G>A）、（c.2057G>A）、（c.2039T>C）、（c.1814C>T）、（c.4049T>C）和（c.734G>A）。
散发性MD患者携带多个参与免疫调节多个步骤的基因变异，这可能使患者在内部应激时通过自身免疫和自身炎症机制易发生炎症。
