Dataset Information

Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss.

ABSTRACT: Connexin26 (Cx26, GJB2) mutations account for >50% of nonsyndromic hearing loss. The deafness is not always congenital. A large group of these patients (?30%) demonstrate a late-onset hearing loss, starting in childhood. They have normal hearing early in life and are therefore good candidates for applying protective and therapeutic interventions. However, the underlying deafness mechanism is unclear. In this study, we used a time-controlled, inducible gene knockout technique to knockout Cx26 expression in the cochlea after birth. We found that deletion of Cx26 after postnatal day 5 (P5) in mice could lead to late-onset hearing loss. Similar to clinical observations, the mice demonstrated progressive, mild to moderate hearing loss. The hearing loss initiated at high frequencies and then extended to the middle- and low-frequency range. The cochlea showed normal development and had no apparent hair cell loss. However, distortion product otoacoustic emission (DPOAE) was reduced. The reduction was also progressive and large at high-frequencies. Consistent with DPOAE reduction, we found that outer hair cell electromotility-associated nonlinear capacitance was shifted to the right and the slope of voltage dependence was reduced. The endocochlear potential was reduced in Cx26 conditional knockout (cKO) mice but the reduction was not associated with progressive hearing loss. These data suggest that Cx26 deficiency may impair active cochlear amplification leading to late-onset hearing loss. Our study also helps develop newer protective and therapeutic interventions to this common nonsyndromic hearing loss.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC4268423 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss.

Zhu Y Y Chen J J Liang C C Zong L L Chen J J Jones R O RO Zhao H-B HB

Neuroscience 20141105

Connexin26 (Cx26, GJB2) mutations account for >50% of nonsyndromic hearing loss. The deafness is not always congenital. A large group of these patients (∼30%) demonstrate a late-onset hearing loss, starting in childhood. They have normal hearing early in life and are therefore good candidates for applying protective and therapeutic interventions. However, the underlying deafness mechanism is unclear. In this study, we used a time-controlled, inducible gene knockout technique to knockout Cx26 exp ...[more]

PMID: 25451287

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Project description:The use of neonatal hearing screening has enabled the identification of congenital unilateral sensorineural hearing loss (USNHL) immediately after birth, and today there are several intervention options available to minimize potential adverse effects of this disease, including cochlear implantation. This study aims to analyze the characteristics of the inner ear of a homogeneous group of congenital non-syndromic USNHL to highlight the features of the inner ear, which can help in clinical, surgical, and rehabilitative decision-making. A retrospective chart review was carried out at a tertiary referral center. Systematic diagnostic work-up and rigorous inclusion-exclusion criteria were applied to 126 children with unilateral hearing impairment, leading to a selection of 39 strictly congenital and non-syndromic USNHL cases, undergoing computed tomography (CT) and magnetic resonance (MR) imaging studies. The frequency and type of malformations of the inner ear in USNHL and unaffected contralateral ears were assessed, with an in-depth analysis of the deficiency of the cochlear nerve (CND), the internal auditory canal (IAC) and the cochlear aperture (CA). Inner ear anomalies were found in 18 out of 39 (46%) of the USNHL patients. In 1 subject, the anomalies were bilateral, and the CND resulted in the predominant identified defect (78% of our abnormal case series), frequently associated with CA stenosis. Only 3 out of 14 children with CND presented stenosis of the IAC. CND and CA stenosis (and to a much lesser extent IAC stenosis) are a frequent association within congenital and non-syndromic USNHL that could represent a distinct pathological entity affecting otherwise healthy infants. In the context of a diagnostic work-up, the evaluation with CT and MRI measurements should take place in a shared decision-making setting with thorough counseling. Both imaging techniques have proven useful in differentiating the cases that will most likely benefit from the cochlear implant, from those with potentially poor implant performance.

Dataset Information

Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss.

Publications

Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss.

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