Screening for Hearing Impairment in Newborns Using Targeted Genomic Sequencing: A Large Pilot Cohort Study

Objectives State-run newborn hearing screening (NBHS) programs have limitations in identifying children with mild or late-onset sensorineural hearing impairment (SNHI). Given that over 50% of pediatric SNHI cases are linked to genetic causes, the increasing accessibility of high-throughput, low-cost...

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Main Authors: Pei-Hsuan Lin, Yu-Ting Chiang, Cheng-Yu Tsai, Chia-Huei Chu, Chia-Cheng Hung, Yi-Ning Su, Wei-Chung Hsu, Tien-Chen Liu, Chuan-Jen Hsu, Po-Nien Tsao, Chen-Chi Wu
Format: Article
Language:English
Published: Korean Society of Otorhinolaryngology-Head and Neck Surgery 2025-05-01
Series:Clinical and Experimental Otorhinolaryngology
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Online Access:http://e-ceo.org/upload/pdf/ceo-2024-00275.pdf
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Summary:Objectives State-run newborn hearing screening (NBHS) programs have limitations in identifying children with mild or late-onset sensorineural hearing impairment (SNHI). Given that over 50% of pediatric SNHI cases are linked to genetic causes, the increasing accessibility of high-throughput, low-cost genomic sequencing may help address these shortcomings. This study investigates the feasibility of integrating a next-generation sequencing (NGS)-based genomic screening protocol into conventional NBHS and examines its potential benefits and challenges. Methods A total of 8,261 newborns underwent simultaneous NBHS and NGS-based genomic screening targeting 46 deafness genes in this prospective study. The subjects’ genotypes were determined, and those with conclusive genetic diagnoses received audiological assessments. Results Conclusive genetic diagnoses were confirmed in 164 subjects, with 112 carrying variants in GJB2 and MTRNR1 and 52 carrying variants in other deafness genes. Notably, 126 of these subjects passed the NBHS, suggesting that an additional 1.5% (126/8,261) of children at risk for SNHI, who would have been missed by conventional physiological screening, can be identified through targeted genomic screening in the general population. Furthermore, one subject’s father, who carried a COL4A5 variant, and three paternal relatives of another subject carrying an EDNRB variant (previously undiagnosed) were identified with Alport and Waardenburg syndromes, respectively, underscoring the familial benefits of this approach. Conclusion Targeted genomic sequencing in newborns may serve as a valuable complement to conventional NBHS by identifying children at risk for SNHI and enabling early diagnosis in families with non-syndromic mimics.
ISSN:1976-8710
2005-0720