Dataset Information

Exploration of molecular genetic etiology for Korean cochlear implantees with severe to profound hearing loss and its implication.

ABSTRACT: Severe to profound sensorineural hearing loss (SNHL) requires cochlear implantation (CI) for auditory rehabilitation. Etiologic diagnoses can contribute to candidacy selection and decision-making regarding the timing of successful CI. However, few studies have been performed to address the etiologic spectrum of severe SNHL in the population where there is no consanguineous marriage and the majority of SNHL cases are sporadic in small sized families. The authors sought to comprehensively understand the etiologies of Korean cochlear implantees by incorporating the targeted resequencing of 204 candidate deafness genes (TRS-204) and a phenotype-driven candidate gene approach.Ninety-three that consented to molecular genetic testing and underwent at least one molecular genetic test were included. Patients with a characteristic Phenotypic marker were subject to Sanger sequencing to detect variants in corresponding candidate genes. The rest of patients without any prominent phenotype were tested on GJB2. Next, TRS-204 was applied in GJB2-negative cases without any phenotypic marker. In addition, the sibling recurrence-risk of SNHL among families with non-diagnostic genotypes after TRS-204 was performed to gain insight of etiologies in non-diagnostic cases.Overall, we could find causative variants in 51 (54.8%) of the 93 cochlear implantees. Thirty (32.3%) probands could be diagnosed by direct Sanger sequencing of candidate genes selected by their phenotypes. GJB2 sequencing added 10 subjects to the group with a diagnostic genotype. TRS-204 could detect a causative variant from additional 11 cases (11.8%). We could not detect any pathogenic deletion or duplication on 204 target genes. The sibling recurrence-risk of SNHL among 42 genetically undiagnosed families with 0.03 (1/38) was significantly lower than among genetically diagnosed recessive families with 0.19 (7/37).Despite that the majority of severe or more degree of SNHL occurs sporadically in Koreans, at least 54.8% of such cases that were willing to join the genetic study in the Korean population are monogenic Mendelian disorders with convincing causative variants. This study also indicates that a substantial portion of unsolved cases after applying our current protocol are predicted to have non-genetic or complex etiology rather than a Mendelian genetic disorder involving new genes beyond the 204 target genes.

SUBMITTER: Park JH

PROVIDER: S-EPMC4243193 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exploration of molecular genetic etiology for Korean cochlear implantees with severe to profound hearing loss and its implication.

Park Joo Hyun JH Kim Nayoung K D NK Kim Ah Reum AR Rhee Jihye J Oh Seung Ha SH Koo Ja-Won JW Nam Jae-Yong JY Park Woong-Yang WY Choi Byung Yoon BY

Orphanet journal of rare diseases 20141106

<h4>Background</h4>Severe to profound sensorineural hearing loss (SNHL) requires cochlear implantation (CI) for auditory rehabilitation. Etiologic diagnoses can contribute to candidacy selection and decision-making regarding the timing of successful CI. However, few studies have been performed to address the etiologic spectrum of severe SNHL in the population where there is no consanguineous marriage and the majority of SNHL cases are sporadic in small sized families. The authors sought to compr ...[more]

PMID: 25373420

Similar Datasets

Project description:ObjectivesThe variability in outcomes of cochlear implantation is largely unexplained, and clinical factors are not sufficient for predicting performance. Genetic factors have been suggested to impact outcomes, but the clinical and genetic heterogeneity of hereditary hearing loss makes it difficult to determine and interpret postoperative performance. It is hypothesized that genetic mutations that affect the neuronal components of the cochlea and auditory pathway, targeted by the cochlear implant (CI), may lead to poor performance. A large cohort of CI recipients was studied to verify this hypothesis.DesignThis study included a large German cohort of CI recipients (n = 123 implanted ears; n = 76 probands) with a definitive genetic etiology of hearing loss according to the American College of Medical Genetics (ACMG)/Association for Molecular Pathology (AMP) guidelines and documented postoperative audiological outcomes. All patients underwent preoperative clinical and audiological examinations. Postoperative CI outcome measures were based on at least 1 year of postoperative audiological follow-up for patients with postlingual hearing loss onset (>6 years) and 5 years for children with congenital or pre/perilingual hearing loss onset (≤6 years). Genetic analysis was performed based on three different methods that included single-gene screening, custom-designed hearing loss gene panel sequencing, targeting known syndromic and nonsyndromic hearing loss genes, and whole-genome sequencing.ResultsThe genetic diagnosis of the 76 probands in the genetic cohort involved 35 genes and 61 different clinically relevant (pathogenic, likely pathogenic) variants. With regard to implanted ears (n = 123), the six most frequently affected genes affecting nearly one-half of implanted ears were GJB2 (21%; n = 26), TMPRSS3 (7%; n = 9), MYO15A (7%; n = 8), SLC26A4 (5%; n = 6), and LOXHD1 and USH2A (each 4%; n = 5). CI recipients with pathogenic variants that influence the sensory nonneural structures performed at or above the median level of speech performance of all ears at 70% [monosyllable word recognition score in quiet at 65 decibels sound pressure level (SPL)]. When gene expression categories were compared to demographic and clinical categories (total number of compared categories: n = 30), mutations in genes expressed in the spiral ganglion emerged as a significant factor more negatively affecting cochlear implantation outcomes than all clinical parameters. An ANOVA of a reduced set of genetic and clinical categories (n = 10) identified five detrimental factors leading to poorer performance with highly significant effects ( p < 0.001), accounting for a total of 11.8% of the observed variance. The single strongest category was neural gene expression accounting for 3.1% of the variance.ConclusionsThe analysis of the relationship between the molecular genetic diagnoses of a hereditary etiology of hearing loss and cochlear implantation outcomes in a large German cohort of CI recipients revealed significant variabilities. Poor performance was observed with genetic mutations that affected the neural components of the cochlea, supporting the "spiral ganglion hypothesis."

Project description:BackgroundTinnitus is defined as the subjective perception of sound in the absence of an external stimulus, and tinnitus disorder becomes relevant when it is associated with emotional distress, cognitive dysfunction, and/or autonomic arousal. Hearing loss is recognized as the main risk factor for the pathogenesis of tinnitus. However, clinical guidelines for tinnitus disorder provide little direction for those who have severe-to-profound hearing loss including those who are pre-lingually Deaf. The aim of this scoping review was to catalogue what is known from the existing literature regarding the experience and management of tinnitus in adults who have a severe-to-profound hearing loss.SummaryA scoping review was conducted following the Preferred Reporting Item for Systematic Reviews and Meta-analysis extension for Scoping Reviews. Records were included if they reported an evaluation of tinnitus in adults who had severe-to-profound hearing loss. The online databases Ovid (MEDLINE, EMBASE and PsycINFO), CINAHL, ProQuest, Scopus, and Google Scholar were searched using the search terms 'tinnitus' (as a MESH term) and 'deaf' OR 'profound hearing loss. Thirty-five records met the inclusion criteria for this review and were cataloged according to three major themes: Impact of tinnitus in deaf adults; Primary treatment of tinnitus in deaf adults; and Cochlear implant studies where tinnitus was a secondary outcome. Tinnitus symptom severity was assessed before and after intervention using tinnitus validated questionnaires in 29 records, with six further records using other assessment tools to measure tinnitus severity. Participants using cochlear implants were included in 30 studies. Medication, repetitive transcranial magnetic stimulation (rTMS), electrical promontory stimulation, and behavioral self-control therapy were each reported in single records.Key messagesThis scoping review cataloged the experience, assessment, and treatment of tinnitus in adults who have severe-to-profound hearing loss. It is shown that there is very limited research reported in this field. Although this review included many records, most focused on the provision of cochlear implants for severe-to-profound hearing loss, with assessment and measurement of tinnitus as a baseline or secondary outcome. Largely missing in the literature are empirical studies that seek firstly to understand the nature of the experience of tinnitus by people with no or little residual access to external sound.

Dataset Information

Exploration of molecular genetic etiology for Korean cochlear implantees with severe to profound hearing loss and its implication.

Publications

Exploration of molecular genetic etiology for Korean cochlear implantees with severe to profound hearing loss and its implication.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets