Audiological Phenotypes of Connexin Gene Mutation Patterns: A Glance at Different GJB2/GJB6 Gene Mutation Profiles

Abstract

GJB2 mutations are the most common cause of autosomal-recessive non-syndromic sensorineural hearing loss (SNHL). The available evidence shows large phenotypic variability across different genotypes and allelic variants. The aim of this study was to investigate the clinical and audiological features of a cohort of subjects with different GJB2/GJB6 gene mutation profiles from a tertiary referral center in Northeastern Italy. We considered 57 patients with GJB2/GJB6 mutations presenting with congenital, non-syndromic SNHL, mainly coming from the Veneto region (Italy). The samples were screened for mutations in exons 1 and 2 of the GJB2 gene and for the GJB6 gene deletion del (GJB6-D13S1830). Free-field and air-conduction frequency-specific thresholds and the pure-tone average (PTA) were considered in the statistical analysis. Five patients (8.87%) had connexin gene mutations in simple heterozygosis, 15 (26.31%) in compound heterozygosis, 34 (59.64%) in homozygosis, and 3 (5.26%) with digenic patterns. The frequency-specific air-conduction thresholds showed significantly different mean values across the different genotypes (Roy's largest-root test, p = 0.0473). Despite the evidence already available on genetic SNHL, many new insights are to be expected. Further large-scale prospective studies including different populations are necessary to confirm these preliminary findings about the clinical and audiological features of patients with different GJB2/GJB6 gene mutation patterns.

Keywords: GJB2/GJB6 gene mutation; audiological phenotype; connexin; genetic hearing loss.

Figure 1

Distribution of GJB2 and GJB6 allelic variants in the considered population.

Figure 2

Violin plots showing the distribution of air-conduction thresholds at 250, 500, 1000, 2000, 4000, and 8000 Hz in the whole sample and across the genotype groups. p-value based on Roy’s largest-root test.

Figure 3

Violin plots showing the distribution of air-conduction PTA variation over time across the genotype groups. p-value is based on MANOVA model, with chi-squared approximation. Simp. het.: simple heterozygosis; Comp. het.: compound heterozygosis; Hom.: homozygosis.