Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Genet Test Mol Biomarkers. 2020 Oct;24(10):674-680. doi: 10.1089/gtmb.2020.0153. Epub 2020 Sep 29.
Hearing loss (HL) is one of the most common and genetically heterogeneous sensory disorders in humans. Genetic causes underlie 50-60% of all HL and the majority of these cases exhibit an autosomal recessive model of inheritance. In our study, we used our targeted custom MiamiOtoGenes panel of 180 HL-associated genes to screen 23 unrelated consanguineous Iranian families with at least two affected children to identify potential causal variants for HL. We identified pathogenic variants in seven genes (, and ) in nine unrelated families with varying HL profiles. These include five reported and four novel mutations. For small consanguineous families that were unsuitable for conventional linkage analysis the employment of the MiamiOtoGenes panel helped identify the genetic cause of HL in a cost-effective and timely manner. This rapid methodology provides for diagnoses of a significant fraction of HL patients, and identifies those who will need more extensive genetic analyses such as whole exome/genome sequencing.
听力损失（HL）是人类最常见且遗传异质性最强的感觉障碍之一。遗传因素导致了 50-60%的 HL，而这些病例中的大多数表现出常染色体隐性遗传模式。在我们的研究中，我们使用了我们的靶向定制的 180 个与 HL 相关基因的 MiamiOtoGenes 面板，对 23 个无血缘关系的伊朗近亲家庭进行了筛查，这些家庭至少有两个受影响的孩子，以确定 HL 的潜在致病变异。我们在 9 个具有不同 HL 特征的无血缘关系的家庭中发现了 7 个基因（,,, 和 ）中的致病性变异。这些变异包括 5 个已报道的和 4 个新的突变。对于不适合传统连锁分析的小近亲家庭，MiamiOtoGenes 面板的使用有助于以具有成本效益和及时的方式确定 HL 的遗传原因。这种快速方法为大量 HL 患者提供了诊断，并确定了那些需要更广泛的遗传分析（如外显子组/基因组测序）的患者。
