Background: Nonsyndromic hearing impairment (NSHI) is the most common type of inherited hearing loss. Mutations in GJB2, which encodes connexin 26, are a major cause worldwide, but their prevalence and variant distribution vary across populations. To systematically evaluate the global prevalence of GJB2 mutations and 5 hotspot variants (c. 35delG, c. 176₁91del16, c. 235delC, c. 299₃00delAT, and c. 109G > A) in NSHI patients, and assess their diagnostic relevance. Methods: A meta-analysis was conducted on studies published between January 2019 and June 2024 retrieved from PubMed, Scopus, Web of Science, and Cochrane Library. Only high-quality studies (Newcastle-Ottawa Scale ≥ 7) with molecular diagnostic data were included. Pooled prevalence, 95% confidence intervals, and heterogeneity (I 2) were calculated. Subgroup and meta-regression analyses were performed according to geographic region. Results: Fifty-one studies from 24 countries covering 18, 968 patients with NSHI were included. The overall prevalence of GJB2 mutations was 25. 9% (95% confidence intervals: 21. 7–30. 1%; I 2 = 96%). The variant-specific rates included c. 235delC (15. 2%), c. 35delG (12. 0%), c. 109G > A (7. 6%), c. 299₃00delAT (3. 1%), and c. 176₁91del16 (0. 7%). The highest prevalence occurred in the Middle East (38. 5%), whereas Africa had the lowest (11. 1%). Conclusion: GJB2 mutations show marked geographic and ethnic variability in populations with NSHI. These findings support region-specific genetic screening to improve the early diagnosis, counseling, and targeted interventions for hereditary hearing loss.
Feng et al. (Fri,) studied this question.