Comprehensive clinical and genetic profiling of Vietnamese pediatric hearing loss: a multi-region exome sequencing study

Congenital hearing loss (HL) in the Vietnamese population remains understudied despite its genetic diversity, limiting our understanding of its genetic etiology and hindering the development of effective, population-specific diagnostic strategies. In this descriptive cross-sectional whole-exome sequencing study, we enrolled 150 children with congenital non-syndromic HL (NSHL) from hospitals and hearing centers across Northern, Central, and Southern Vietnam to describe the genetic landscape of HL and provide new insights into rare and HL-associated variants. Clinical variant annotation was performed for 1589 deafness-associated genes, focusing on pathogenic, likely pathogenic, and variants of uncertain significance. Genetic factors strongly associated with NSHL accounted for 7.33% (11 of 150) of moderate-to-profound HL cases, involving both autosomal dominant and autosomal recessive inheritance patterns. Four variants across three genes were identified, namely GJB2:c.235del (p.L79CfsTer3), GJB2:c.109G > A (p.V37I), COCH:c.538C > T (p.R180Ter), and MYO6:c.2751dup (p.Q918TfsTer24). Two of these variants demonstrated a trend toward disease enrichment within the cohort, with the highest minor allele frequency (MAF) observed in GJB2:c.109G > A at 11%, followed by MYO6:c.2751dup at 2%. Although GJB2:c.235del showed a relatively high MAF of 1.3%, the observed minor alleles did not differ significantly from those in the East Asian and KHV control populations. These findings reveal distinct clinical and molecular profiles of congenital HL, providing essential knowledge for the development of targeted screening and diagnostic strategies tailored to the Vietnamese pediatric population.