Clinical utility of exome sequencing in hearing loss: A retrospective cohort study

Chang Liu¹Yanlin Huang²Anpeng Fu²Yunan Wang²Jing Wu²Yan Zhang²Li Du²Hongke Ding²Lihua Yu²Fake Li²YIMING QI²Yuan Liu²Xingwang Wang²Yukun Zeng²Ling Liu²Ying Xiong²Yuanling Liu²Xin Zhao²Liyuan Fang²Jiayi Jian²Aihua Yin²Yanqin You^3*

• ¹Guangdong Province Women and Children Hospital, Guangzhou, China
• ²Guangdong Women and Children Hospital, Guangzhou, China
• ³1st Medical Center of Chinese PLA General Hospital, Beijing, China

Background: Hearing loss (HL) is a prevalent sensorineural disorder with a highly heterogeneous etiology. Next generation sequencing (NGS) has revolutionized genetic testing landscape for diseases characterized by high genetic and allelic heterogeneity, enabling the simultaneous screening of hundreds of genes. Methods: One hundred and seventy-one unrelated patients with non-syndromic or syndromic HL were enrolled. Exome sequencing (ES) was applied to explore molecular etiology in the cohort, and clinical reports were returned by geneticists and genetic counselors. Multidisciplinary team forums were conducted for accurate diagnoses and improved patient management. Results: The molecular cause of HL was determined in 78 of 171 probands (45.6%), 54 with an autosomal recessive (AR) inheritance pattern, 23 with an autosomal dominant (AD) pattern, and one with both AR/AD inheritance patterns. Candidate variants in 33 genes were identified in the study cohort, 14 with AR inheritance pattern, 18 with AD pattern, and one with AR/AD inheritance pattern. Twenty-eight of the variants identified in the study were novel. Conclusion: Exome sequencing facilitates genetic diagnosis and improves the management of patients with HL in the clinical practice. Identifying the etiology of HL may improve the management of patients with HL, refine genetic counseling and facilitate the estimation of likelihood of recurrence.