Targeted sequencing identifies 33 novel mutations in 130 ClinGen curated hearing loss genes among 253 pediatric patients: A retrospective case study.

Hearing loss (HL) can occur at any age, with hereditary HL being one of the most prevalent congenital disabilities. In the present study, a cohort of pediatric patients with HL was established, comprising 259 individuals at the Children's Hospital of Zhejiang University from 2017-2022. All patients underwent comprehensive diagnostic evaluations, including complete clinical examinations and audiological assessments. Targeted genomic enrichment with massively parallel sequencing was applied to analyze the mutation spectrum of known hearing-loss genes in 253 Chinese children who had positive hearing screening results. Among the 253 patients, 211 (83.40%) exhibited bilateral HL, while 42 (16.60%) had unilateral HL. Targeted sequencing identified 197 variants in 104 genes, yielding a detection rate of 41.1%. A total of 144 genotypes were identified, including 62 heterozygous mutations, 6 hemizygous mutations, 23 homozygous mutations and 48 complex heterozygous mutations. The four most frequently identified genes were (26.5%), (13.5%), (6.5%) and (6.5%). Additionally, 33 novel variants in deafness-associated genes were discovered, comprising 21 novel pathogenic or likely pathogenic variants and 12 variants of uncertain significance. The present results highlight the genetic profile of HL in the Chinese population, with GJB2 being the most prevalent causative gene in early-onset deafness. Furthermore, the current findings provide insight into age- or severity-related gene frequencies for HL. For the genetically unsolved cases, further investigation into digenic inheritance models or other contributing factors is warranted.