Integrated hearing and genetic screening for neonatal deafness in a resource-limited region: insights from Qingyuan, China

ObjectiveThis study aimed to delineate the prevalence and mutation spectrum of deafness-associated genes among newborns in a resource-limited region of China, and to assess the diagnostic yield of combined hearing and genetic screening.MethodsFrom May 2017 to May 2023, 22,819 newborns underwent concurrent hearing screening and genetic screening for deafness-associated mutations using 9-variant or 23-variant microarrays targeting GJB2, SLC26A4, GJB3, and mitochondrial 12SrRNA. Whole-exome sequencing was performed in selected cases with inconclusive results. All infants were followed until 2.5 years of age.ResultsHearing screening confirmed hearing loss in 25 infants (0.11%). Genetic screening identified 994 (4.36%) mutation carriers, predominantly GJB2 (3.31%) and SLC26A4 (0.78%). Among 351 GJB2 109G>A heterozygotes, all had normal hearing at 2.5 years. Among 43 homozygotes, 7 (16.28%) had congenital deafness; the rest remained normal. All 42 mitochondrial mutation carriers remained deafness-free after preventive education. The 23-variant panel detected 24.73% positive cases (225-fold vs. hearing alone). WES resolved 80% of ambiguous cases.ConclusionGJB2 and SLC26A4 are the predominant deafness genes in this region. Combined screening identifies distinct risk groups, heterozygotes for reproductive counselling, mitochondrial carriers for prevention, and homozygotes for early intervention. Long-term follow-up of normal-hearing homozygotes showed low short-term delayed-onset risk.