Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with hearing loss in clinical practice

Int J Pediatr Otorhinolaryngol. 2022 Oct:161:111258. doi: 10.1016/j.ijporl.2022.111258. Epub 2022 Jul 31.

Abstract

Background: Hearing loss (HL) is a prevalent sensorineural disorder, and is among the most etiologically heterogeneous disorders. With the advent of next-generation sequencing (NGS) technologies, hundreds of candidate genes can be analyzed simultaneously in a cost-effective manner.

Methods: Ninety-four patients from 87 families diagnosed with non-syndromic or syndromic HL were enrolled. A custom-designed HL panel and clinical exome sequencing (CES) were applied to explore molecular etiology in the cohort, and the efficacy of the two panels was examined.

Results: The etiologic diagnosis for HL has been identified for 36 out of 87 probands (41.4%), 28 with an autosomal recessive (AR) inheritance pattern and 8 with an autosomal dominant (AD) pattern. Candidate variants in 18 different genes were identified in the study cohort, 10 with AR inheritance pattern and 8 with AD pattern. Fourteen of the variants identified in the study were novel.

Conclusions: The custom-designed HL panel covers almost all known HL-associated genes, and can be used as an effective clinical diagnostic platform; CES evaluates all exons related to clinical symptoms, and is also suitable for clinical diagnosis of HL. Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with HL in the clinical practice.

Keywords: Clinical evaluation; Hearing loss; Molecular analysis; Next-generation sequencing.

MeSH terms

  • Cohort Studies
  • Deafness*
  • Exome Sequencing
  • Hearing Loss* / diagnosis
  • Hearing Loss* / genetics
  • Hearing Loss* / therapy
  • Hearing Loss, Sensorineural* / diagnosis
  • Hearing Loss, Sensorineural* / genetics
  • Hearing Loss, Sensorineural* / therapy
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mutation
  • Pedigree