Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
BGI Genomics, BGI-Shenzhen, Shenzhen, 518083, China.
Sci Rep. 2021 Feb 17;11(1):4036. doi: 10.1038/s41598-021-83493-6.
Hearing loss is one of the most common birth disorders in humans, with an estimated prevalence of 1-3 in every 1000 newborns. This study investigates the molecular etiology of a hearing loss cohort using a stepwise strategy to effectively diagnose patients and address the challenges posed by the genetic heterogeneity and variable mutation spectrum of hearing loss. In order to target known pathogenic variants, multiplex PCR plus next-generation sequencing was applied in the first step; patients which did not receive a diagnosis from this were further referred for exome sequencing. A total of 92 unrelated patients with nonsyndromic hearing loss were enrolled in the study. In total, 64% (59/92) of the patients were molecularly diagnosed, 44 of them in the first step by multiplex PCR plus sequencing. Exome sequencing resulted in eleven diagnoses (23%, 11/48) and four probable diagnoses (8%, 4/48) among the 48 patients who were not diagnosed in the first step. The rate of secondary findings from exome sequencing in our cohort was 3% (2/58). This research presents a molecular diagnosis spectrum of 92 non-syndromic hearing loss patients and demonstrates the benefits of using a stepwise diagnostic approach in the genetic testing of nonsyndromic hearing loss.
听力损失是人类最常见的出生缺陷之一，估计每 1000 名新生儿中就有 1-3 名患有听力损失。本研究采用逐步策略调查听力损失队列的分子病因，以有效诊断患者，并解决听力损失的遗传异质性和可变突变谱带来的挑战。为了针对已知的致病性变异，在第一步中应用了多重 PCR 加下一代测序；未通过该方法进行诊断的患者则进一步进行外显子组测序。本研究共纳入了 92 名非综合征型听力损失的无亲缘关系患者。共有 64%（59/92）的患者通过分子手段得到了诊断，其中 44 例在第一步的多重 PCR 加测序中得到了诊断。在外显子组测序中，在未在第一步中得到诊断的 48 名患者中，有 11 例得到了诊断（23%，11/48）和 4 例可能的诊断（8%，4/48）。外显子组测序在我们的队列中发现的次要发现率为 3%（2/58）。本研究展示了 92 名非综合征型听力损失患者的分子诊断谱，并证明了在非综合征型听力损失的基因检测中使用逐步诊断方法的益处。
