Disparities in deafness gene mutations between Han and Li ethnic newborns in Hainan, China: insights from a combined screening program

Abstract Objective This study aimed to investigate the spectrum of deafness gene variants among newborns in Hainan Province, China. We also evaluated the effectiveness of a combined hearing and genetic screening approach in this region. Special attention was given to differences between the Han and Li populations, as well as the relationship between genetic variants and hearing follow-up outcomes. Methods From October 2020 to June 2022, 2128 newborns in Hainan (1502 Han, 626 Li) received combined hearing and genetic screening. Hearing screening followed national standards. Genetic screening was carried out using targeted next-generation sequencing of GJB2 , SLC26A4 , GJB3 , and MT-RNR1 . Infants with detected variants or those referred from hearing screening received diagnostic audiological follow-up. Results Among the 2128 newborns (1502 Han, 626 Li), 514 (24.15%) carried deafness gene variants. Variants in GJB2 were the most common, with a carrier rate of 22.51% (479/2128). The GJB2 c.109G > A (p.V37I) variant was the hotspot variant, with an overall carrier rate of 20.91% (445/2128). This rate was significantly higher in the Li ethnic group (28.6%, 179/626) than in the Han group (17.7%, 266/1502; P < 0.01). Thirty-seven newborns carried biallelic pathogenic variants in GJB2 . Nine newborns (0.42%) were diagnosed with hearing loss at three months, and all 9 had biallelic GJB2 variants (7 homozygous c.109G > A, 1 compound heterozygote c.109G > A/299_300del, and 1 homozygous c.235del). Longitudinal follow-up of children with biallelic c.109G > A variants showed delayed-onset and progressive hearing loss, with confirmed cases increasing at ages 2 and 4. There are no significant differences in mean ABR thresholds or their standard deviations between Han and Li individuals with homozygous GJB2 c.109G > A mutations at 4 years of age. For patients with biallelic c.109G > A variants, the current setting of ABR thresholds may lead to missed diagnosis. Conclusion This study showed a high prevalence of deafness gene variants, especially GJB2 c.109G > A, among newborns in Hainan, with clear ethnic differences. Combined screening was effective in identifying genetic hearing loss, including delayed-onset and progressive cases that could be missed by hearing screening alone. These findings support adding genetic screening to regional newborn screening programs and highlight the need for long-term monitoring of at-risk children.