The genetic background of Ménière's disease (MD) was studied in one patient with childhood‐onset MD and his grandfather affected with middle age–onset MD. Whole‐exome sequencing was performed and the data were compared to 76 exomes from unrelated subjects without MD. Thirteen rare inner ear expressed variants with pathogenic estimations were observed in the case of childhood‐onset MD. These variants were in genes involved in the formation of cell membranes or the cytoskeleton and in genes participating in cell death or gene‐regulation pathways. His grandfather shared two of the variants: p.Y273N in HMX2 and p.L229F in TMEM55B. HMX2 p.Y273N was considered the more likely candidate for MD, as the gene is known to affect both hearing and vestibular function. The variant in the HMX2 gene may affect inner ear development and structural integrity and thus might predispose to the onset of MD. As there was a significant difference in onset between the patients, an accumulation of defects in several pathways is probably responsible for the exceptionally early onset of the disease, and the genetic etiology of childhood‐onset MD is most likely multifactorial. This is the first molecular genetic study of childhood‐onset MD.

中文翻译：

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全外显子组测序表明儿童期梅尼埃病的多等位基因遗传

梅尼埃病 (MD) 的遗传背景在一名儿童期发病的 MD 患者及其祖父中年发病的 MD 中进行了研究。进行了全外显子组测序，并将数据与来自没有 MD 的无关受试者的 76 个外显子组进行了比较。在儿童发病的 MD 病例中观察到 13 种具有致病性估计的罕见内耳表达变异。这些变异存在于参与细胞膜或细胞骨架形成的基因以及参与细胞死亡或基因调控途径的基因中。他的祖父分享了两个变体：HMX2 中的 p.Y273N 和 TMEM55B 中的 p.L229F。HMX2 p.Y273N 被认为更可能是 MD 的候选者，因为已知该基因会影响听力和前庭功能。HMX2 基因中的变异可能会影响内耳发育和结构完整性，因此可能易患 MD。由于患者之间的发病率存在显着差异，多种途径中缺陷的累积可能是该疾病异常早期发病的原因，而儿童期发病的 MD 的遗传病因很可能是多因素的。这是首次对儿童期发病的 MD 进行分子遗传学研究。