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

INTRODUCTION: The contribution of Gap junction beta-2 protein (GJB2) to the genetic load of deafness and its mutation spectra vary among different ethnic groups. OBJECTIVE: In this study, the mutation spectrum and audiologic features of patients with GJB2 mutations were evaluated with a specific focus on residual hearing. METHODS: 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. GJB2 sequencing was carried out for 130 probands with sporadic or autosomal recessive non syndromic hearing loss. The audiograms were evaluated in the GJB2 mutants. RESULTS: Of the 130 subjects, 22 (16.9%) were found to carry at least one mutant allele of GJB2. The c.235delC mutation was shown to have the most common allele frequency (39.0%) among GJB2 mutations, followed by p.R143W (26.8%) and p.V37I (9.8%). Among those probands without the p.V37I allele in a trans 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. CONCLUSION: 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.