Genotype and Phenotype Analyses of a Novel Variant (c.2512C>T p.(Pro838Ser)) Associated with DFNA6/14/38.

The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch-German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband.

Electrically evoked auditory cortical responses elicited from individually fitted stimulation parameters in cochlear implant users.

Objective: To investigate electrically evoked auditory cortical responses (eACR) elicited from the stimulation of intracochlear electrodes based on individually fitted stimulation parameters in cochlear implant (CI) users.

Design: An eACR setup based on individual fitting parameters is proposed. A 50-ms alternating biphasic pulse train was used to stimulate apical, medial, and basal electrodes and to evoke auditory cortical potentials (N1-P2 complex).

Genotype-Phenotype Correlations of Pathogenic Variants in DFNA9: A HuGE Systematic Review and Audiometric Meta-Analysis.

Pathogenic missense variants in are associated with DFNA9, an autosomal dominantly inherited type of progressive sensorineural hearing loss with or without vestibular dysfunction. This study is a comprehensive overview of genotype-phenotype correlations using the PRISMA and HuGENet guidelines. Study characteristics, risk of bias, genotyping and data on the self-reported age of onset, symptoms of vestibular dysfunction, normative test results for vestibular function, and results of audiovestibular examinations were extracted for each underlying pathogenic variant.

A retrospective cohort study exploring the association between different mitochondrial diseases and hearing loss.

Some pathogenic variants in mtDNA and nuclear DNA, affecting mitochondrial function, are associated with hearing loss. Behavioral and electrophysiological auditory performance are obtained from 62 patients, clinically diagnosed with different mitochondrial diseases (MD) using tone/speech audiometry and Auditory Brainstem Responses (ABR). Audiological variables (hearing loss type, pure tone average (PTA), interaural asymmetry, speech perception and brainstem neural conductivity) were analyzed and related to Newcastle Mitochondrial Disease Scale for Adults (NMDAS).

Intracorporeal Cortical Telemetry as a Step to Automatic Closed-Loop EEG-Based CI Fitting: A Proof of Concept.

Electrically evoked auditory potentials have been used to predict auditory thresholds in patients with a cochlear implant (CI). However, with exception of electrically evoked compound action potentials (eCAP), conventional extracorporeal EEG recording devices are still needed. Until now, built-in (intracorporeal) back-telemetry options are limited to eCAPs.

Auditory brainstem response prior to MRI compared to standalone MRI in the detection of vestibular schwannoma: A modelling study.

Objectives: To determine the cost-effectiveness of auditory brainstem response prior to MRI (ABR-MRI) compared to standalone MRI to diagnose vestibular schwannoma.

Design: A state transition model was developed to simulate costs and effects (quality-adjusted life years [QALY]) for both diagnostic strategies for patients suspected of a vestibular schwannoma. Model input was derived from literature, hospital databases and expert opinions.

Use of an Extra-Tympanic Membrane Electrode to Record Cochlear Microphonics with Click, Tone Burst and Chirp Stimuli.

This study determined electrocochleography (ECochG) parameter settings to obtain cochlear microphonics (CM) with less invasive flexible extra-tympanic membrane electrodes. In 24 adult normal-hearing subjects, CMs were elicited by presenting click stimuli at 100 dBnHL, tone bursts (2 kHz) and broadband (BB) CE-chirps LS (Interacoustics, Middelfart, Denmark), both at 80 dBnHL. Different high-pass filters (HPFs) (3.

A Novel COCH Mutation Affects the vWFA2 Domain and Leads to a Relatively Mild DFNA9 Phenotype.

Objective: To study the genotype and phenotype of a Dutch family with autosomal dominantly inherited hearing loss.

Study Design: Genotype-phenotype correlation study. Genetic analysis consisted of linkage analysis, variable number of tandem repeats analysis, and Sanger sequencing.

Impact of cochlear implantation on the function of the three semicircular canals.

Objective: To assess the effect of cochlear implantation on the function of the semicircular canals (SCC) and on experienced vestibular symptoms. Second, to determine the relation between vestibular test results.

Design: Retrospective cohort study assessing absolute and categorised results of caloric irrigation test, video Head Impulse Test (vHIT) and Dizziness Handicap Inventory (DHI) before and after cochlear implantation.

A in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss.

Background: Hearing loss is one of the most prevalent disabilities worldwide, and has a significant impact on quality of life. The adult-onset type of the condition is highly heritable but the genetic causes are largely unknown, which is in contrast to childhood-onset hearing loss.

Methods: Family and cohort studies included exome sequencing and characterisation of the hearing phenotype.

The P300 auditory event-related potential as a method to assess the benefit of contralateral hearing aid use in bimodal listeners: a proof-of-concept.

Bimodal listeners vary in the amount of benefit they receive from wearing the contralateral hearing aid. This may partially depend on the listener's auditory processing capacities. The current study explores whether the P300 event-related potential can provide insight into the mechanisms underlying the benefits of wearing a contralateral hearing aid.

De novo and inherited loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment.

ATP2B2 encodes the PMCA2 Ca pump that plays an important role in maintaining ion homeostasis in hair cells among others by extrusion of Ca from the stereocilia to the endolymph. Several mouse models have been described for this gene; mice heterozygous for loss-of-function defects display a rapidly progressive high-frequency hearing impairment. Up to now ATP2B2 has only been reported as a modifier, or in a digenic mechanism with CDH23 for hearing impairment in humans.

MPZL2, Encoding the Epithelial Junctional Protein Myelin Protein Zero-like 2, Is Essential for Hearing in Man and Mouse.

In a Dutch consanguineous family with recessively inherited nonsyndromic hearing impairment (HI), homozygosity mapping combined with whole-exome sequencing revealed a MPZL2 homozygous truncating variant, c.72del (p.Ile24Metfs22).

Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction.

Unraveling the causes and pathomechanisms of progressive disorders is essential for the development of therapeutic strategies. Here, we identified heterozygous pathogenic missense variants of LMX1A in two families of Dutch origin with progressive nonsyndromic hearing impairment (HI), using whole exome sequencing. One variant, c.

A Comparison of Surgical Treatments for Superior Semicircular Canal Dehiscence: A Systematic Review.

Objective: We investigate the postoperative subjective and objective outcomes of different surgical treatments for superior semicircular canal dehiscence (SSCD): vestibular signs, auditory signs, vestibular evoked myogenic potential test, pure tone audiogram, speech audiogram, or video-nystagmography.

Data Sources: An electronic search performed in the PubMed, Cochrane Library, and EMBASE databases on 15th of September 2015. A systematic search was conducted.

The effect of device use after sequential bilateral cochlear implantation in children: An electrophysiological approach.

Objectives: In many studies evaluating the effect of sequential bilateral cochlear implantation in congenitally deaf children, device use is not taken into account. In this study, however, device use was analyzed in relation to auditory brainstem maturation and speech recognition, which were measured in children with early-onset deafness, 5-6 years after bilateral cochlear implantation. We hypothesized that auditory brainstem maturation is mostly functionally driven by auditory stimulation and is therefore influenced by device use and not mainly by inter-implant delay.

Age-Related Changes in Binaural Interaction at Brainstem Level.

Objectives: Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction.

Similar phenotypes caused by mutations in OTOG and OTOGL.

Objectives: Recently, OTOG and OTOGL were identified as human deafness genes. Currently, only four families are known to have autosomal recessive hearing loss based on mutations in these genes. Because the two genes code for proteins (otogelin and otogelin-like) that are strikingly similar in structure and localization in the inner ear, this study is focused on characterizing and comparing the hearing loss caused by mutations in these genes.

Auditory cortical maturation in children with sequential bilateral cochlear implants.

Objective: To assess the effect of sequential bilateral cochlear implantation on auditory, cortical maturation after various periods of unilateral cochlear implant use.

Study Design: Prospective cohort study.

Setting: Tertiary academic referral center.

Hippocampal dysfunction in the Euchromatin histone methyltransferase 1 heterozygous knockout mouse model for Kleefstra syndrome.

Euchromatin histone methyltransferase 1 (EHMT1) is a highly conserved protein that catalyzes mono- and dimethylation of histone H3 lysine 9, thereby epigenetically regulating transcription. Kleefstra syndrome (KS), is caused by haploinsufficiency of the EHMT1 gene, and is an example of an emerging group of intellectual disability (ID) disorders caused by genes encoding epigenetic regulators of neuronal gene activity. Little is known about the mechanisms underlying this disorder, prompting us to study the Euchromatin histone methyltransferase 1 heterozygous knockout (Ehmt1(+/-)) mice as a model for KS.

Prediction of vestibular schwannoma growth: a novel rule based on clinical symptomatology.

Objectives: The aim of this study was to formulate a predictive rule for vestibular schwannoma growth during the initial observation period after diagnosis.

Methods: Logistic regression models were fitted, with tumor growth in the first year as the dependent variable and patient characteristics as the independent variables. Backward selection was used to eliminate superfluous predictors.

Cervical dystonia after ear surgery.

Background: The pathophysiology of primary focal dystonia remains insufficiently understood, but may be explained by a 'double-lesion' model, in which a particular trigger on top of an intrinsic susceptibility due to a certain genetic predisposition can induce dystonia.

Case-report: Here, we describe a patient who developed cervical dystonia soon after ear surgery (revision stapedectomy), which had caused vestibular hypofunction.

Discussion: We also discuss other cases of dystonia associated with vestibular lesions and with other reported triggers, and put these into the context of the possible pathophysiology.

Electrically evoked auditory brainstem responses in children with sequential bilateral cochlear implants.

Objective: To examine the effect of sequential bilateral cochlear implantation on auditory brainstem maturation and the effect of age in receiving the second implant (CI2).

Study Design: Prospective cohort study.

Setting: Tertiary academic referral center.

ATP8B1 is essential for maintaining normal hearing.

ATP8B1 deficiency is caused by autosomal recessive mutations in ATP8B1, which encodes the putative phospatidylserine flippase ATP8B1 (formerly called FIC1). ATP8B1 deficiency is primarily characterized by cholestasis, but extrahepatic symptoms are also found. Because patients sometimes report reduced hearing capability, we investigated the role of ATP8B1 in auditory function.