Bianco-Bortoletto Giselle, Almeida-Carneiro Geovana, Fabbri-Scallet Helena, Parra-Perez Alberto M, Lopes Karen de Carvalho, Vieira Tatiana de Almeida Lima Sá, Ganança Fernando Freitas, Amor-Dorado Juan Carlos, Soto-Varela Andres, Lopez-Escamez Jose A, Sartorato Edi Lucia
Meniere Disease Neuroscience Research Program, Faculty of Medicine & Health, School of Medical Sciences, The Kolling Institute, University of Sydney, Sydney, NSW 2064, Australia.
Laboratory of Human Molecular Genetics, Center for Molecular Biology and Genetic Engineering-CBMEG, State University of Campinas-UNICAMP, Campinas 13083-875, SP, Brazil.
Genes (Basel). 2025 May 28;16(6):654. doi: 10.3390/genes16060654.
Ménière's Disease (MD) is a chronic inner ear disorder defined by recurring episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and/or fullness in the ear. Its prevalence varies by region and ethnicity, with scarce epidemiological data in the Brazilian population. Although most MD cases are sporadic, familial MD (FMD) is observed in 5% to 20% of European cases. Through exome sequencing, we have found a rare missense variant in the gene in a Brazilian individual with MD with probable European ancestry (chr11:17599671C>T), which was previously reported in a Spanish cohort. Two additional rare missense heterozygous variants were found in the same proband. Splice Site analysis showed that chr11:17599671C>T may lead to substantial changes generating exonic cis regulatory elements, and protein modelling revealed structural changes in the presence of chr11:17599671C>T, chr11:17576581G>C, and chr11:17594108C>T, predicted to highly destabilize the protein structure. The manuscript aims to replicate genes previously reported in a Spanish cohort, and the main finding is that a Brazilian patient with MD also has variants previously reported in familial MD, supporting as the most frequently mutated gene in MD.
梅尼埃病（MD）是一种慢性内耳疾病，其特征为反复发作的眩晕、波动性感音神经性听力损失、耳鸣和/或耳部胀满感。其患病率因地区和种族而异，巴西人群的流行病学数据稀少。尽管大多数MD病例为散发性，但在欧洲5%至20%的病例中观察到家族性MD（FMD）。通过外显子组测序，我们在一名可能有欧洲血统的巴西MD患者中发现了该基因中的一种罕见错义变异（chr11:17599671C>T），该变异先前在一个西班牙队列中已有报道。在同一先证者中还发现了另外两种罕见的错义杂合变异。剪接位点分析表明，chr11:17599671C>T可能导致产生外显子顺式调控元件的实质性变化，蛋白质建模显示在存在chr11:17599671C>T、chr11:17576581G>C和chr11:17594108C>T的情况下蛋白质结构发生变化，预计会高度破坏蛋白质结构的稳定性。该手稿旨在复制先前在一个西班牙队列中报道的基因，主要发现是一名巴西MD患者也有先前在家族性MD中报道的变异，支持该基因是MD中最常发生突变的基因。
