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Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS.

ABSTRACT: Genetic factors, the most common etiology in severe to profound hearing loss, are one of the key determinants of Cochlear Implantation (CI) and Electric Acoustic Stimulation (EAS) outcomes. Satisfactory auditory performance after receiving a CI/EAS in patients with certain deafness gene mutations indicates that genetic testing would be helpful in predicting CI/EAS outcomes and deciding treatment choices. However, because of the extreme genetic heterogeneity of deafness, clinical application of genetic information still entails difficulties. Target exon sequencing using massively parallel DNA sequencing is a new powerful strategy to discover rare causative genes in Mendelian disorders such as deafness. We used massive sequencing of the exons of 58 target candidate genes to analyze 8 (4 early-onset, 4 late-onset) Japanese CI/EAS patients, who did not have mutations in commonly found genes including GJB2, SLC26A4, or mitochondrial 1555A>G or 3243A>G mutations. We successfully identified four rare causative mutations in the MYO15A, TECTA, TMPRSS3, and ACTG1 genes in four patients who showed relatively good auditory performance with CI including EAS, suggesting that genetic testing may be able to predict the performance after implantation.

SUBMITTER: Miyagawa M

PROVIDER: S-EPMC3794008 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS.

Miyagawa Maiko M Nishio Shin-ya SY Ikeda Takuo T Fukushima Kunihiro K Usami Shin-ichi S

PloS one 20131009 10

Genetic factors, the most common etiology in severe to profound hearing loss, are one of the key determinants of Cochlear Implantation (CI) and Electric Acoustic Stimulation (EAS) outcomes. Satisfactory auditory performance after receiving a CI/EAS in patients with certain deafness gene mutations indicates that genetic testing would be helpful in predicting CI/EAS outcomes and deciding treatment choices. However, because of the extreme genetic heterogeneity of deafness, clinical application of g ...[more]

PMID: 24130743

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Project description:BackgroundAdults with single sided deafness (SSD) have lost binaural function, which limits sound source localization, speech understanding in noise, and quality of life. For SSD patients, restoration of bilateral auditory input is possible only with a cochlear implant (CI). In this study, cortical auditory evoked potentials (CAEPs) and behavioral performance were measured in left-implanted (SSD-CI-L) and right-implanted (SSD-CI-R) patients before and after cochlear implantation. We hypothesized that improvements in behavioral performance would be accompanied by changes in CAEPs after cochlear implantation.DesignProspective longitudinal study.SettingTertiary referral center.MethodNine right-handed adult SSD CI patients participated in the study. CAEPs were recorded before cochlear implantation and at 6 and 12 months post-implantation. CAEPs were elicited using speech stimuli (/ba/) delivered in sound field at 70 dBA. Global field power (GFP) latency and amplitude were calculated for P1, N1 and P2 peaks at each test session. CAEP were analyzed at frontocentral (Cz) and temporal (P7, P8, T7 and T8) and mastoid electrodes (M1 and M2) contralateral to the CI ear. Behavioral measures (sentence recognition in noise, with and without spatial cues) were collected at the same test sessions as for CAEPs. Speech performance and CAEPs were also measured in a control group of normal-hearing (NH) subjects.ResultsWhile increased N1 amplitude was observed in the scalp potential maps for GFP and Cz for SSD-CI-L patients after implantation, the changes were not statistically significant. Peak CAEP amplitude at electrodes to contralateral to the CI ear increased after cochlear implantation for all SSD-CI patients, but significant increases were observed only for mastoid sites. Peak latencies for some components at temporal and mastoid sites remained significantly longer than for the NH control group, even after cochlear implantation. For SSD-CI-R patients, P2 peak amplitude for baseline GFP and Cz was significantly lower than for the NH control group. A significant improvement for speech understanding in noise was observed at 12 months post-implantation when speech was presented to the CI ear and noise to the non-implanted ear.ConclusionAfter cochlear implantation, speech understanding significantly improved when speech and noise were spatially separated. The increased N1 amplitude for SSD-CI-L patients and the increased bilateral activation for all SSD-CI patients may reflect cortical reorganization and restoration of binaural function after one year of experience with the CI. However, because of the limited number of SSD patients, significant changes in cortical activity after cochlear implantation were often difficult to observe.

Project description:ImportanceIn 2019, the US Food and Drug Administration approved cochlear implantation for children with single-sided deafness (SSD). The absence of robust clinical data specific to pediatric patients to guide shared decision-making and to identify potential advantages is a challenge in family counseling.ObjectiveTo evaluate the audiological and patient-reported outcomes in children who underwent cochlear implantation for SSD and to assess the association between time of implantation, subjective outcomes, and cochlear implant device use rates.Data sourceMEDLINE, Embase, Scopus, Cochrane, and PubMed were searched for English-language articles that were published in a peer-reviewed journal from database inception to February 18, 2020.Study selectionInclusion criteria were designed to capture studies that evaluated pediatric patients (1) younger than 18 years, (2) with a diagnosis of SSD for which they underwent a cochlear implantation, and (3) with at least 1 outcome of interest measured numerically: speech perception, sound localization, device use, and patient-reported outcomes. Of the 526 articles reviewed, 12 (2.3%) met the selection criteria.Data extraction and synthesisThe Meta-analyses Of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed. Data were pooled using fixed-effect and random-effect models. The following information was obtained from each article: study characteristics, patient characteristics, hearing loss and intervention characteristics, and outcomes.Main outcomes and measuresOutcomes were (1) postoperative changes in speech perception (in quiet was measured as a proportion of correct responses, and in noise was measured as decibel signal to noise ratio for speech reception threshold) and sound localization (measured in degree of localization error), (2) patient-reported audiological outcomes (measured by the speech, spatial, and qualities of hearing scale), and (3) device use rates among children who received cochlear implantation for SSD.ResultsTwelve observational studies that evaluated 119 children (mean [SD] age, 6.6 [4.0] years) with SSD who received a cochlear implant were included. Most children showed clinically meaningful improvement in speech perception in noise (39 of 49 children [79.6%]) and in quiet (34 of 42 children [81.0%]). Long duration of deafness (>4 years in congenital SSD and >7 years in perilingual SSD) was the most commonly proposed reason for lack of improvement. Sound localization as measured by degrees of error from true location (mean difference [MD], -24.78°; 95% CI, -34.16° to -15.40°; I2 = 10%) improved statistically significantly after cochlear implantation. Patients with acquired SSD and shorter duration of deafness compared with those with congenital SSD reported greater improvements in speech (MD, 2.27; 95% CI, 1.89-2.65 vs 1.58; 95% CI, 1.00-2.16) and spatial (MD, 2.95; 95% CI, 2.66-3.24 vs 1.68; 95% CI, 0.96-2.39) hearing qualities. The duration of deafness among device nonusers was statistically significantly longer than the duration of deafness among regular device users (median difference, 6.84; 95% CI, 4.02-9.58).Conclusions and relevanceThis systematic review and meta-analysis found that cochlear implantation for children with SSD was associated with clinically meaningful improvements in audiological and patient-reported outcomes; shorter duration of deafness may lead to better outcomes. These findings can guide future research efforts, refine cochlear implantation candidacy criteria, and aid in family counseling and shared decision-making.

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Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS.

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Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS.

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