PDF(Pubmed)
Abstract：
Meniere disease (MD) is a debilitating disorder of the inner ear defined by sensorineural hearing loss (SNHL) associated with episodes of vertigo and tinnitus. Severe tinnitus, which occurs in around 1% of patients, is a multiallelic disorder associated with a burden of rare missense single nucleotide variants in synaptic genes. Rare structural variants (SVs) may also contribute to MD and severe tinnitus. In this study, we analyzed exome sequencing data from 310 MD Spanish patients and selected 75 patients with severe tinnitus based on a Tinnitus Handicap Inventory (THI) score > 68. Three rare deletions were identified in two unrelated individuals overlapping the ERBB3 gene in the positions: NC_000012.12:g.56100028_56100172del, NC_000012.12:g.56100243_56101058del, and NC_000012.12:g.56101359_56101526del. Moreover, an ultra-rare large duplication was found covering the AP4M1, COPS6, MCM7, TAF6, MIR106B, MIR25, and MIR93 genes in another two patients in the NC_000007.14:g.100089053_100112257dup region. All the coding genes exhibited expression in brain and inner ear tissues. These results confirm the contribution of large SVs to severe tinnitus in MD and pinpoint new candidate genes to get a better molecular understanding of the disease.
摘要：
梅尼埃病（MD）是由与眩晕和耳鸣发作相关的感觉神经性听力损失（SNHL）定义的内耳衰弱性疾病。严重耳鸣,大约1%的患者发生这种情况，是一种多等位基因疾病，与突触基因中罕见的错义单核苷酸变异有关。罕见的结构变体（SV）也可能导致MD和严重耳鸣。在这项研究中,我们分析了310例MD西班牙患者的外显子组测序数据,并根据耳鸣障碍量表(THI)评分>68选择了75例重度耳鸣患者.在两个无关的个体中发现了三个罕见的缺失，这些个体在以下位置与ERBB3基因重叠：NC_000012.12：g.56100028_56100172del，NC_000012.12:g.56100243_56101058del,和NC_000012.12：g.56101359_56101526del。此外，发现覆盖AP4M1，COPS6，MCM7，TAF6，MIR106B，MIR25和MIR93基因在另外两名患者的NC_000007.14：g.100089053_100112257dup区域。所有编码基因在脑和内耳组织中均有表达。这些结果证实了大SVs对MD中严重耳鸣的贡献，并确定了新的候选基因以更好地了解该疾病。
