Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Center for Statistical Genetics, Department of Neurology, Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA.
Eur J Hum Genet. 2019 Sep;27(9):1456-1465. doi: 10.1038/s41431-019-0417-2. Epub 2019 May 3.
Hearing impairment (HI) is characterized by extensive genetic heterogeneity. To determine the population-specific contribution of known autosomal recessive nonsyndromic (ARNS)HI genes and variants to HI etiology; pathogenic and likely pathogenic (PLP) ARNSHI variants were selected from ClinVar and the Deafness Variation Database and their frequencies were obtained from gnomAD for seven populations. ARNSHI prevalence due to PLP variants varies greatly by population ranging from 96.9 affected per 100,000 individuals for Ashkenazi Jews to 5.2 affected per 100,000 individuals for Africans/African Americans. For Europeans, Finns have the lowest prevalence due to ARNSHI PLP variants with 9.5 affected per 100,000 individuals. For East Asians, Latinos, non-Finish Europeans, and South Asians, ARNSHI prevalence due to PLP variants ranges from 17.1 to 33.7 affected per 100,000 individuals. ARNSHI variants that were previously reported in a single ancestry or family were observed in additional populations, e.g., USH1C p.(Q723*) reported in a Chinese family was the most prevalent pathogenic variant observed in gnomAD for African/African Americans. Variability between populations is due to how extensively ARNSHI has been studied, ARNSHI prevalence and ancestry specific ARNSHI variant architecture which is impacted by population history. Our study demonstrates that additional gene and variant discovery studies are necessary for all populations and particularly for individuals of African ancestry.
听力障碍（HI）的特征是广泛的遗传异质性。为了确定已知常染色体隐性非综合征（ARNS）HI 基因和变体对 HI 病因的人群特异性贡献；从 ClinVar 和聋病变异数据库中选择致病性和可能致病性（PLP）ARNSHI 变体，并从 gnomAD 获得七个人群的变体频率。PLP 变体引起的 ARNSHI 患病率因人群而异，从每 10 万人中有 96.9 人受影响的阿什肯纳兹犹太人到每 10 万人中有 5.2 人受影响的非洲/非裔美国人。对于欧洲人来说，芬兰人由于 ARNSHI PLP 变体而导致的患病率最低，每 10 万人中有 9.5 人受影响。对于东亚人、拉丁美洲人、非芬兰欧洲人和南亚人，由于 PLP 变体导致的 ARNSHI 患病率在每 10 万人中有 17.1 至 33.7 人受影响。在单一血统或家庭中先前报道过的 ARNSHI 变体在其他人群中也有观察到，例如，在一个中国家庭中报道的 USH1C p.(Q723*)是在 gnomAD 中观察到的最常见的致病性变体，在非洲/非裔美国人中。人群之间的变异性归因于 ARNSHI 研究的广泛程度、ARNSHI 患病率以及受人群历史影响的特定 ARNSHI 变体结构。我们的研究表明，所有人群，特别是非洲裔人群，都需要进行额外的基因和变体发现研究。
