Residual Hearing in DFNB1 Deafness and Its Clinical Implication in a Korean Population

<div><p>Introduction</p><p>The contribution of Gap junction beta-2 protein (<i>GJB2</i>) to the genetic load of deafness and its mutation spectra vary among different ethnic groups.</p><p>Objective</p><p>In this study, the mutation spectrum and audiologic features of patients with <i>GJB2</i> mutations were evaluated with a specific focus on residual hearing.</p><p>Methods</p><p>An initial cohort of 588 subjects from 304 families with varying degrees of hearing loss were collected at the otolaryngology clinics of Seoul National University Hospital and Seoul National University Bundang Hospital from September 2010 through January 2014. <i>GJB2</i> sequencing was carried out for 130 probands with sporadic or autosomal recessive non syndromic hearing loss. The audiograms were evaluated in the <i>GJB2</i> mutants.</p><p>Results</p><p>Of the 130 subjects, 22 (16.9%) were found to carry at least one mutant allele of <i>GJB2</i>. The c.235delC mutation was shown to have the most common allele frequency (39.0%) among <i>GJB2</i> mutations, followed by p.R143W (26.8%) and p.V37I (9.8%). Among those probands without the p.V37I allele in a <i>trans</i> configuration who showed some degree of residual hearing, the mean air conduction thresholds at 250 and 500 Hz were 57 dB HL and 77.8 dB HL, respectively. The c.235delC mutation showed a particularly wide spectrum of hearing loss, from mild to profound and significantly better hearing thresholds at 250 Hz and 2k Hz than in the non-p.V37I and non-235delC nonsyndromic hearing loss and deafness 1(DFNB1) subjects.</p><p>Conclusion</p><p>Despite its reputation as the cause of severe to profound deafness, c.235delC, the most frequent DFNB1 mutation in our cohort, caused a wide range of hearing loss with some residual hearing in low frequencies. This finding can be of paramount help for prediction of low frequency hearing thresholds in very young DFNB1 patients and highlights the importance of soft surgery for cochlear implantation in these patients.</p></div

Overlapping audiograms of the patients with c.235delC and non-c.235delC <i>GJB2</i> mutations.

<p>A. Patients with hearing loss caused by a c.235delC mutation (excluding patients with a p.V37I mutation in the <i>trans</i> configuration) (n = 13). B. Patients with hearing loss caused by a non-c.235delC mutation (excluding patients with a p.V37I mutation in the <i>trans</i> configuration) (n = 5). Detailed lists of non-c.235delC mutations are p.R143W homozygote, p.R143W single heterozygote, p.Glu47* and p.Ala171Glufs*40 compound heterozygote, and p.T86R and p.R143W compound heterozygote. (*p = 0.05, **p = 0.03, by the Mann-Whitney U test) (Black dots mean hearing thresholds of each subject, which may represent more than one subject with identical hearing thresholds. Red dots represent mean hearing thresholds of each frequency).</p

<i>GJB2</i> mutations and their allele frequencies.

<p><i>GJB2</i> mutations and their allele frequencies.</p

Overlapping audiograms of all patients with <i>GJB2</i> mutations.

<p>All of the patients with hearing loss caused by <i>GJB2</i> mutations in this study (n = 22). (Black dots mean hearing thresholds of each subject, which may represent more than one subject with identical hearing thresholds. Red dots represent mean hearing thresholds of each frequency).</p

<i>GJB2</i> mutants and their hearing levels in this study.

<p>(*average of 500, 1000, and 2000 Hz)</p><p>(†average of 250, 500, 1000 Hz)</p><p><i>GJB2</i> mutants and their hearing levels in this study.</p

MOESM1 of Strong founder effect of p.P240L in CDH23 in Koreans and its significant contribution to severe-to-profound nonsyndromic hearing loss in a Korean pediatric population

Additional file 1. Lists of the genes included in the three targeted panel