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Introduction: Several studies have associated congenital sensorineural hearing loss in children with prolongation of the cardiac parameter QTc. The cause of this association is unknown. At the same time, mutations in GJB2, which encodes connexin 26, are the most common cause of congenital hearing impairment., Objective: To compare electrocardiographic parameters (PR interval, QRS complex, and QTc interval) in patients with hearing loss who were tested for mutations in GJB2 and GJB6 to investigate whether these mutations affect electrical activity of the heart., Methods: 346 patients (176 males, 170 females) with sensorineural hearing loss of 30dB HL or more, aged 21.8±19.9 years (including 147 children <14 years), underwent both genetic study for GJB2 and GJB6 mutations and electrocardiography., Results: Mutations in GJB2, including homozygotes and heterozygotes, were found in 112 (32%) patients. There were no significant differences in ECG parameters between groups of patients with and without mutations in GJB2. No differences were observed either in men (mean PR with mutation: 155±16.6 vs. 153.6±30.1 without; QRS: 99.9±9.9 vs. 101.1±15.4; QTc: 414.9±29.9 vs. 412.4±25.7) or women (mean PR with: 148.7±21 vs. 143.8±22.8 without; QRS: 94.8±7.6 vs. 92.9±9.6; QTc: 416.8±20.6 vs. 424.9±22.8). In similar fashion, we did we find any significant differences between groups of children with and without GJB2 mutations (mean PR with: 126.3±19.6 vs. 127±19.7 without; QRS: 80.7±9.5 vs. 79.4±11.6; QTc: 419.7±23.5 vs. 419.8±24.8)., Conclusion: No association was found between the presence of GJB2 mutations encoding connexin 26 in patients with hearing loss and their ECG parameters (PR, QRS, QTc)., (Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Hereditary hearing loss (HL) is a very heterogeneous trait, with 46 gene identifications for non-syndromic HL. Mutations in GJB2 cause up to half of all cases of severe-to-profound congenital autosomal recessive non-syndromic HL, with 35delG being the most frequent mutation in Caucasians. Although a genotype-phenotype correlation has been established for most GJB2 genotypes, the HL of 35delG homozygous patients is mild to profound. We hypothesise that this phenotypic variability is at least partly caused by the influence of modifier genes. By performing a whole-genome association (WGA) study on 35delG homozygotes, we sought to identify modifier genes. The association study was performed by comparing the genotypes of mild/moderate cases and profound cases. The first analysis included a pooling-based WGA study of a first set of 255 samples by using both the Illumina 550K and Affymetrix 500K chips. This analysis resulted in a ranking of all analysed single-nucleotide polymorphisms (SNPs) according to their P-values. The top 250 most significantly associated SNPs were genotyped individually in the same sample set. All 192 SNPs that still had significant P-values were genotyped in a second independent set of 297 samples for replication. The significant P-values were replicated in nine SNPs, with combined P-values between 3 x 10(-3) and 1 x 10(-4). This study suggests that the phenotypic variability in 35delG homozygous patients cannot be explained by the effect of one major modifier gene. Significantly associated SNPs may reflect a small modifying effect on the phenotype. Increasing the power of the study will be of greatest importance to confirm these results.

Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P<.0001). The HI of 48 different genotypes was less severe than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mild-to-moderate HI (median 25-40 dB). Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes.