Prevalence of GJB2 gene mutations in nonsyndromic hearing impairments: A systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: 25.9% pooled prevalence

• Primary Outcome: Overall GJB2 mutation prevalence in nonsyndromic hearing impairment

• Nnt Or Sensitivity: Diagnostic yield varies by region: Middle East 38.5%, Africa 11.1%; c.235delC most common variant at 15.2%

• Confidence Interval: 95% CI: 21.7-30.1%

Clinical Application

Genetic testing for GJB2 mutations is readily available in Australian pathology services Relevant for Australian genetic counselling services and may inform PBS-funded genetic testing protocols. Aligns with RACGP guidelines for hereditary hearing loss assessment and family planning counselling Patients with nonsyndromic hearing impairment requiring genetic counselling and molecular diagnosis

Abstract

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.176_191del16, c.235delC, c.299_300delAT, 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 (I2) 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%; I2 = 96%). The variant-specific rates included c.235delC (15.2%), c.35delG (12.0%), c.109G > A (7.6%), c.299_300delAT (3.1%), and c.176_191del16 (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.

References

1. 1.Feng, R., Mangantig, E., Wan Yusoff, W. S., Li, H., Li, X., & Abu, M. N. (2026). Prevalence of GJB2 gene mutations in nonsyndromic hearing impairments: A systematic review and meta-analysis. Medicine, 105(22), e48877. https://doi.org/10.1097/MD.0000000000048877