Mutation Spectrum of Common Pathogenic Genes in Hereditary Hearing Loss: A Literature Review

School of Basic Medical Sciences, Zhengzhou University, No. 100 Kexue Avenue, Zhengzhou, Henan, China

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Hereditary hearing loss constitutes one of the most prevalent sensory disorders globally, affecting approximately 466 million individuals, with genetic factors accounting for 50-60% of congenital and early-onset cases across more than 120 identified causative genes that present substantial challenges for accurate molecular diagnosis and personalized clinical management. This review systematically synthesizes current evidence regarding the mutation spectrum characteristics of common pathogenic genes implicated in both non-syndromic and syndromic hereditary hearing loss, with particular emphasis on population-specific distribution patterns and genotype-phenotype correlations derived from recent high-quality studies published between 2020 and 2024. The comprehensive analysis demonstrates that GJB2 and SLC26A4 represent the most frequently implicated genes in non-syndromic hearing loss, while MYO7A and USH2A predominate in Usher syndrome cases, with hotspot mutations exhibiting remarkable ethnic heterogeneity attributable to founder effects and historical population migrations, as exemplified by the predominance of GJB2 c.35delG in European populations versus GJB2 c.235delC in East Asian populations. Next-generation sequencing technologies have achieved diagnostic yields ranging from 18% to 48.6%, depending on patient selection criteria, enabling implementation of population-specific tiered genetic testing strategies that optimize diagnostic efficiency while facilitating informed clinical decisions regarding intervention timing, cochlear implantation candidacy, and reproductive counseling. Interpretation of mutation spectrum data remains constrained by heterogeneity in study designs, variable sequencing methodologies, and underrepresentation of certain ethnic populations in existing cohorts, warranting cautious extrapolation across diverse clinical settings.