This study aimed to analyse the distribution and genotype-phenotype correlations of pathogenic variants among 11 509 newborns carrying at least one common deafness-associated variant.
A genotype distribution analysis was performed on 11 509 neonates identified as carriers of ≥1 pathogenic variant across four common deafness genes (GJB2, SLC26A4, MT-RNR1 and GJB3) at our centre between January 2022 and December 2024. Hearing outcomes were assessed through a comprehensive evaluation protocol, initial screening (>48 hour after birth, before discharge), re-screening at 42 days and diagnostic evaluation by 3 months. Sanger sequencing identified potential compound heterozygous variants, and genotype-phenotype analysis was performed on infants with hearing loss (HL).
Among the 11 509 newborns carrying ≥1 pathogenic variant, two high-risk groups were identified: 653 newborns (5.67%) carrying biallelic pathogenic variants in GJB2 and 113 newborns (0.98%) carrying the MT-RNR1 m.1555A>G or m.1494C>T variants. However, only 58 infants were confirmed with HL, and 15.52% of these passed the initial hearing screening. Sanger sequencing reclassified 23.08% of presumed heterozygotes with HL as compound heterozygotes. Acoustic diagnostic results showed that GJB2 c.235del homozygotes exhibited higher HL incidence (50% vs 6.51%) and more severe/profound HL (66.67% vs 7.14%) than GJB2 c.109G>A homozygotes.
Our data demonstrated that while genetic screening readily identifies infants with hereditary deafness susceptibility, newborn hearing screening fails to detect most of these high-risk cases due to the absence or delayed onset of HL. This gap obligates long-term audiological monitoring and highlights genetic testing’s critical role in enabling early surveillance for later-onset HL.