Postlingual Hearing Loss Research Articles

Reorganization of auditory-visual network interactions in long-term unilateral postlingual hearing loss

Long-term unilateral hearing loss could reorganize the functional network association between the bilateral auditory cortices, while alterations of other functional networks need to be further explored. We attempted to investigate the pattern of the reorganization of functional network associations between the auditory and visual cortex caused by long-term postlingual unilateral hearing loss (UHI) and its relationship with clinical characteristics. Therefore, 48 patients with hearing loss caused by unilateral acoustic tumors and 52 matched healthy controls were enrolled, and their high-resolution structural MRI and resting-state functional MRI data were also collected to depict the brain network. Degree centrality (DC) was employed to evaluate the functional network association of the auditory-visual network interaction. Group comparisons were performed to investigate the network reorganization, and its correlations with clinical data were calculated. Compared with the healthy control group, patients with UHI showed significantly increased DC between the auditory network (superior temporal gyrus and the medial geniculate body) and the visual network. Meanwhile, this difference was positively correlated with the extent of hearing impairment, and the correlation was more significant with the ipsilateral superior temporal gyrus in cases of acoustic neuroma. These results suggest that long-term unilateral hearing impairment may lead to enhancement of the visual-auditory network interactions and that the degree of reorganization is positively correlated with the pure tone average (PTA) and is more significant for the ipsilateral superior temporal gyrus, which provides clinical evidence regarding cross-modal plasticity in the UHI and its lateralization.

The impact of cochlear implantation on health-related quality of life in older adults, measured with the Health Utilities Index Mark 2 and Mark 3.

To determine the usefulness of the Health Utilities Index (HUI) in older cochlear implant (CI) recipients, the primary aims were: (1) to assess health-related quality of life (HRQoL), measured with HUI, in older CI candidates while comparing with age- and gender-matched normal-hearing controls; (2) to compare HRQoL after CI with the pre-operative situation, using HUI and the Nijmegen cochlear implant questionnaire (NCIQ). The difference between pre- and postoperative speech intelligibility in noise (SPIN) and in quiet (SPIQ) and the influence of pre-operative vestibular function on HRQoL in CI users were also studied. Twenty CI users aged 55years and older with bilateral severe-to-profound postlingual sensorineural hearing loss and an age- and gender-matched normal-hearing control group were included. HRQoL was assessed with HUI Mark 2 (HUI2), HUI Mark 3 (HUI3) and NCIQ. The CI recipients were evaluated pre-operatively and 12months postoperatively. HUI3 Hearing (p = 0.02), SPIQ (p < 0.001), SPIN (p < 0.001) and NCIQ (p = 0.001) scores improved significantly comparing pre- and postoperative measurements in the CI group. No significant improvement was found comparing pre- and postoperative HUI3 Multi-Attribute scores (p = 0.07). The HUI3 Multi-Attribute score after CI remained significantly worse (p < 0.001) than those of the control group. Vestibular loss was significantly related to a decrease in HUI3 Multi-Attribute (p = 0.037) and HUI3 Emotion (p = 0.021) scores. The HUI is suitable to detect differences between normal-hearing controls and CI users, but might underestimate HRQoL changes after CI in CI users over 55.

Phenotypic Heterogeneity of Post-lingual and/or Milder Hearing Loss for the Patients With the GJB2 c.235delC Homozygous Mutation

ObjectiveTo report the phenotypic heterogeneity of GJB2 c.235delC homozygotes associated with post-lingual and/or milder hearing loss, and explore the possible mechanism of these unconditional phenotypes.MethodsMutation screening of GJB2 was performed on all ascertained members from Family 1006983 and three sporadic patients by polymerase chain reaction (PCR) amplification and Sanger sequencing. Next generation sequencing (NGS) was successively performed on some of the affected members and normal controls from Family 1006983 to explore additional possible genetic codes. Reverse transcriptase–quantitative PCR was conducted to test the expression of Connexin30.ResultsWe identified a Chinese autosomal recessive hearing loss family with the GJB2 c.235delC homozygous mutation, affected members from which had post-lingual moderate to profound hearing impairment, and three sporadic patients with post-lingual moderate hearing impairment, instead of congenital profound hearing loss. NGS showed no other particular variants. Overexpression of Connexin30 in some of these cases was verified.ConclusionPost-lingual and/or moderate hearing impairment phenotypes of GJB2 c.235delC homozygotes are not the most common phenotype, revealing the heterogeneity of GJB2 pathogenic mutations. To determine the possible mechanism that rescues part of the hearing or postpones onset age of these cases, more cases are required to confirm both Connexin30 overexpression and the existence of modifier genes.

Outcome of cochlear implantation in the worse ear of post-lingual asymmetric hearing loss: elucidation of prognostic markers

Background Specific correlations between the outcomes of cochlear implantation (CI) and hearing thresholds of the both ears in post-lingual asymmetric hearing loss (AHL) patients were not clear. Aims/Objectives To identify the variables influencing the outcome of CI in post-lingual AHL patients. Method We included 18 adult subjects who had CI in the worse ear due to post-lingual AHL with average hearing asymmetry of 36 dB. Speech perception scores were evaluated in the sound field with hearing aid on the better ear before CI, and with the cochlear implant in the worse ear at 3, 6, and 12 months after CI switch-on. Results Average increases in phonetically balanced word score, spondee word score, and everyday sentence score at 12 months from CI switch-on compared with those before CI were 38.9%p, 46.2%p, and 52.4%p, respectively. Multiple linear regression analysis showed that speech perception scores were negatively influenced by age at implantation and hearing threshold difference of both ears (HTD-Both) itself, rather than the worse or better ear hearing thresholds. Conclusions and significance Post-lingual AHL subjects with high average hearing asymmetry can benefit from CI in the worse ear, while CI outcomes can be adversely influenced by HTD-Both and age at implantation both in the short- and long-term follow-up.

Genotype-phenotype correlation in patients with Usher syndrome and pathogenic variants in MYO7A: implications for future clinical trials.

PurposeWe aimed to establish correlations between the clinical features of a cohort of Usher syndrome (USH) patients with pathogenic variants in MYO7A, type of pathogenic variant, and location on the protein domain.MethodsSixty‐two USH patients from 46 families with biallelic variants in MYO7A were examined for visual and audiological features. Participants were evaluated based on self‐reported ophthalmological history and ophthalmological investigations (computerized visual field testing, best‐corrected visual acuity, and ophthalmoscopic and electrophysiological examination). Optical coherence tomography and fundus autofluorescence imaging were performed when possible. Auditory and vestibular functions were evaluated. Patients were classified according to the type of variant and the protein domain where the variants were located.ResultsMost patients displayed a typical USH1 phenotype, that is, prelingual severe‐profound sensorineural hearing loss, prepubertal retinitis pigmentosa (RP) and vestibular dysfunction. No statistically significant differences were observed for the variables analysed except for the onset of hearing loss due to the existence of two USH2 cases, defined as postlingual sensorineural hearing loss, postpubertal onset of RP, and absence of vestibular dysfunction, and one atypical case of USH.ConclusionWe were unable to find a correlation between genotype and phenotype for MYO7A. However, our findings could prove useful for the assessment of efficacy in clinical trials, since the type of MYO7A variant does not seem to change the onset, severity or course of visual disease.

A novel missense mutation in SMPX causes a rare form of X-linked postlingual sensorineural hearing loss in a Chinese family.

BackgroundX-linked deafness-4 (DFNX4) caused by the functional loss of the SMPX gene is one form of nonsyndromic hearing loss with postlingual onset. This study aimed to investigate the cause of X-linked inherited sensorineural nonsyndromic hearing loss in a four-generation Chinese family and to explain the reason for extremely different hearing phenotypes between the proband and other family members.MethodsWhole-exome sequencing (WES) and co-segregation analysis were used to identify the pathogenic variants. Furthermore, methylation differences among the androgen receptor genes were utilized to investigate whether the severe phenotype of the proband is related to X-chromosome inactivation (Xi).ResultsWe described in detail the clinical characteristics of the family and identified a novel missense mutation (c.262C>G: p.Gln88Glu) in SMPX by WES. This variant was co-segregated with the postlingual hearing loss phenotype and was absent in 300 normal controls. Also, we found that the proband, a 4-year-old female, carries two new compound heterozygous mutations (c.9259G>A: p.Val3087Ile and c.8576G>A: p.Arg2859His) in the USH2A gene, but to date without any other symptoms except profound sensorineural hearing loss. Additionally, analysis of X-chromosome inactivation indicated moderate skewing in the proband, which is probably related to the heterogeneity of clinical characteristics.ConclusionsThis is the first study to report a missense mutation of SMPX in a Chinese family. Our findings have enriched the mutation and phenotypic spectrum of the SMPX gene.

Impact of Cochlear Implantation on Neurocognitive Subdomains in Adult Cochlear Implant Recipients

Introduction: Age-related hearing loss affects about one-third of the population worldwide. Studies suggest that hearing loss may be linked to cognitive decline and auditory rehabilitation may improve cognitive functions. So far, the data are limited, and the underlying mechanisms are not fully understood. The study aimed to analyze the impact of cochlear implantation on cognition in a large homogeneous population of hearing-impaired adults using a comprehensive non-auditory cognitive assessment with regard to normal-hearing (NH) subjects. Material and Methods: Seventy-one cochlear implant (CI) candidates with a postlingual, bilateral severe or profound hearing loss aged 66.3 years (standard deviation [SD] 9.2) and 105 NH subjects aged 65.96 years (SD 9.4) were enrolled. The computer-based neurocognitive tool applied included 11 subtests covering attention (M3), short- and long-term memory (recall and delayed recall), working memory (0- and 2-back, Operation Span [OSPAN] task), processing speed (Trail Making Test [TMT] A), mental flexibility (TMT B), inhibition (cFlanker and iFlanker), and verbal fluency. CI patients underwent a neurocognitive testing preoperatively as well as 12 months postoperatively. Impact of hearing status, age, gender, and education on cognitive subdomains was studied. Additionally, after controlling for education and age, cognitive performance of CI subjects (n = 41) was compared to that of NH (n = 34). Results: CI users achieved significantly better neurocognitive scores 12 months after cochlear implantation than before in most subtests (M3, [delayed] recall, 2-back, OSPAN, iFlanker, and verbal fluency; all p < 0.05) except for the TMT A and B. A significant correlation could be found between the postoperative improvement in speech perception and in the attentional task M3 (p = 0.01). Hearing status (p = 0.0006) had the strongest effect on attention, whereas education had a high impact on recall (p = 0.002), OSPAN (p = 0.0004), and TMT A (p = 0.005) and B (p = 0.003). Inhibition was mainly age-dependent with better results in younger subjects (p = 0.016). Verbal fluency was predicted by gender as females outperformed men (p = 0.009). Even after controlling for age and education NH subjects showed a significantly better performance than CI candidates in the recall (p = 0.03) and delayed recall (p = 0.01) tasks. Postoperatively, there was no significant difference between the 2 groups anymore. Conclusion: Impact of cochlear implantation on neurocognitive functions differs according to the cognitive subdomains. Postoperatively, CI recipients performed as good as age- and education-matched NH subjects.

A synonymous variant in MYO15A enriched in the Ashkenazi Jewish population causes autosomal recessive hearing loss due to abnormal splicing.

Nonsyndromic hearing loss is genetically heterogeneous. Despite comprehensive genetic testing, many cases remain unsolved because the clinical significance of identified variants is uncertain or because biallelic pathogenic variants are not identified for presumed autosomal recessive cases. Common synonymous variants are often disregarded. Determining the pathogenicity of synonymous variants may improve genetic diagnosis. We report a synonymous variant c.9861 C > T/p.(Gly3287=) in MYO15A in homozygosity or compound heterozygosity with another pathogenic or likely pathogenic MYO15A variant in 10 unrelated families with nonsyndromic sensorineural hearing loss. Biallelic variants in MYO15A were identified in 21 affected and were absent in 22 unaffected siblings. A mini-gene assay confirms that the synonymous variant leads to abnormal splicing. The variant is enriched in the Ashkenazi Jewish population. Individuals carrying biallelic variants involving c.9861 C > T often exhibit progressive post-lingual hearing loss distinct from the congenital profound deafness typically associated with biallelic loss-of-function MYO15A variants. This study establishes the pathogenicity of the c.9861 C > T variant in MYO15A and expands the phenotypic spectrum of MYO15A-related hearing loss. Our work also highlights the importance of multicenter collaboration and data sharing to establish the pathogenicity of a relatively common synonymous variant for improved diagnosis and management of hearing loss.

Predictive models for cochlear implant outcomes: Performance, generalizability, and the impact of cohort size.

While cochlear implants have helped hundreds of thousands of individuals, it remains difficult to predict the extent to which an individual’s hearing will benefit from implantation. Several publications indicate that machine learning may improve predictive accuracy of cochlear implant outcomes compared to classical statistical methods. However, existing studies are limited in terms of model validation and evaluating factors like sample size on predictive performance. We conduct a thorough examination of machine learning approaches to predict word recognition scores (WRS) measured approximately 12 months after implantation in adults with post-lingual hearing loss. This is the largest retrospective study of cochlear implant outcomes to date, evaluating 2,489 cochlear implant recipients from three clinics. We demonstrate that while machine learning models significantly outperform linear models in prediction of WRS, their overall accuracy remains limited (mean absolute error: 17.9-21.8). The models are robust across clinical cohorts, with predictive error increasing by at most 16% when evaluated on a clinic excluded from the training set. We show that predictive improvement is unlikely to be improved by increasing sample size alone, with doubling of sample size estimated to only increasing performance by 3% on the combined dataset. Finally, we demonstrate how the current models could support clinical decision making, highlighting that subsets of individuals can be identified that have a 94% chance of improving WRS by at least 10% points after implantation, which is likely to be clinically meaningful. We discuss several implications of this analysis, focusing on the need to improve and standardize data collection.

Congenital Hereditary Endothelial Dystrophy with Valvular Heart Disease: A Case Report

Background: Congenital hereditary endothelial dystrophy (CHED) is a rare disease of the corneal endothelium. It is a nonprogressive clouding of the corneal, presenting at birth in most cases or shortly after it. This disease is categorized as an autosomal recessive disorder, which manifests with diffuse corneal edema, Descemet membrane thickening, and lack of endothelial cells. The primary abnormality in CHED is a degeneration of endothelial cells during or after the fifth month of gestation. The literature review has shown that CHED can occur with progressive, postlingual sensorineural hearing loss in Harboyan syndrome; however, it is not associated with any systemic abnormality. Case report: Our study reports a case of CHED and valvular heart disease in a neonate. To the best of our knowledge, no research has been performed to investigate the relationship between CHED and valvular heart disease. In addition, the patient’s mother had vaginal discharge in the fifth month of gestation, which was, as stated in the previous studies, the period during which the abnormality occurs in CHED. The two aforementioned issues highlight the need for performing the present study. Conclusion: Occurrence of CHED and heart disease has not been reported, there is a need for more research into this subject.

Comparative Performance of Lateral Wall and Perimodiolar Cochlear Implant Arrays.

The physical shape of cochlear implant (CI) arrays may impact hearing outcomes. The goal of this study was to compare post-operative speech and melody perception between patients with lateral wall (LW) and perimodiolar (PM) electrode arrays across a range of lengths and manufacturers. Retrospective chart review. Tertiary Care Hospital. 119 adult patients with post-lingual hearing loss who underwent cochlear implantation. A total of seven different electrodes were evaluated including 5 different LW electrodes (CI422 [Cochlear American], 1J [Advanced Bionics], Medium [Med El], Standard [Med El], Flex28 [Med El]) and 2 PM electrodes (Contour [Cochlear American], MidScala [Advanced Bionics]). Speech perception outcomes (n = 119 patients) were measured by Consonant-Nucleus-Consonant (CNC) scores collected 3, 6, 12 and 24 months after implantation. Melody perception outcomes (n = 35 CI patients and n = 6 normal hearing patients) were measured by Melodic Contour Identification (MCI). CNC scores increased over time after implantation across all array designs. PM designs exhibited higher CNC scores compared to LW electrodes, particularly 6-months after implantation. Pre-operative pure tone averages did not correlate with post-operative CNC scores. PM arrays outperformed LW electrodes in terms of MCI scores. The physical shape of cochlear implant electrode arrays may impact hearing performance. Compared to LW designs, PM arrays appear to offer superior speech perception during the first 6 months after implantation, with performance equalizing between groups by 24 months. Compared to LW designs, PM arrays also appear to afford superior melody perception.

The outcome of various amplification strategies in post-lingual sensorineural hearing loss patients

Abstract:Objective: to measure functional and audiologic outcomes in patient with severe to profound post-lingual sensorineural hearing loss using either binaural hearing aids, unilateral cochlear implant or bimodal hearing.Method: This observational cross-sectional study was conducted on 60 adult patients with post-lingual bilateral severe to profound SNHL with age range from 20-50 years divided into 3 equal groups; Group I: 20 patients using binaural regular powerful hearing aids, Group II: 20 patients with unilateral cochlear implant and Group III: 20 patients using bimodal hearing strategy. The functional outcome was measured by using the Categorical Auditory Performances (CAP) scale which is ranged from 0 to 7. The auditory outcome was measured by aided audiometry threshold and clear speech perception test.Results: The CAP score showed higher score in group III as compared to the other groups and the number of participants with CAP score 5 and above was 0 in group I, 6 (30 %) in group II and 12 (60 %) in group III. This was a highly statistically significant difference in mean aided threshold among the 3 groups 42.5, 37.5 and 21.67 respectively. This was a highly statistically significant difference between the three groups in clear speech perception with increased performance in group III in both quiet and variable noisy situations. Conclusion & Recommendations:Bimodal hearing is beneficial when there is a good selection and good optimization of the fitting criteria of the HA. Our study recommends putting guidelines for bimodal candidacy which maximize patient benefits.

Isolated Incudostapedial Cholesteatomas: Unique Radiologic and Surgical Features

Congenital cholesteatomas originate from epithelial tissue present within the middle ear in patients with an intact tympanic membrane, no history of otologic surgery, otorrhea, or tympanic membrane perforation. They are diagnosed by a pearl-like lesion on otoscopy and computed tomography (CT) scan showing an expansile soft-tissue mass. We describe a series of patients with no prior otologic history presenting with progressive unilateral conductive hearing loss and normal otoscopy. The CT scans showed ossicular erosion without obvious soft-tissue mass. Surgery confirmed incudostapedial erosion found to be cholesteatoma. In this study, we characterize the clinical course of patients diagnosed with isolated incudostapedial cholesteatoma (IIC) and review possible pathologic mechanisms. Retrospective review of IIC cases treated by the Department of Pediatric Otolaryngology, Rady Children's Hospital, San Diego, 2014 to 2020. Data included patient demographics, clinical features, imaging, surgical findings, and audiologic data. Five patients were diagnosed with IIC (3 [60%] female; mean age at presentation 10.7 years [range 5.5-16.0]). All patients presented with postlingual unilateral conductive hearing loss and normal otoscopy without any past otologic history; delay in diagnosis ranged from 4 months to several years. The CT scans showed ossicular chain erosion with an absent long process of the incus and/or stapes superstructure. All patients underwent middle ear exploration, revealing a thin layer of cholesteatoma in the incudostapedial region, confirmed by histopathology. Mean preoperative speech reception threshold was 55 dB and improved to a mean of 31 dB in the 4 patients who underwent ossicular chain reconstruction. Isolated incudostapedial cholesteatoma should be included as a possible etiology in pediatric patients with insidious onset of unilateral conductive hearing loss with normal otoscopy, unremarkable otologic history, and a CT scan showing ossicular abnormality/disruption without notable middle ear mass. These patients should be counseled preoperatively regarding the possibility of cholesteatoma and should undergo middle ear exploration with possible ossiculoplasty.

Does Cochlear Implantation Affect Openness-to-Experience in Profound Postlingual Hearing Loss?

Recent studies suggest that hearing loss in postlingually deafened adults may be associated with lowered levels of the personality factor Openness to experience. This study investigated whether cochlear implantation in postlingually deafened adults raises the level of Openness to experience. Fifty-five postlingually deafened adults (mean age: 63years) were assessed with the Neuroticism-Extraversion-Openness-Five-Factor-Inventory (NEO-FFI), a questionnaire capturing the five personality factors Extraversion, Openness to experience, Neuroticism, Agreeableness, and Conscientiousness. Personality assessment occurred before cochlear implantation and 24months after implant activation. On factors Extraversion, Neuroticism, Agreeableness, and Conscientiousness the mean scores of the sample were equal to population norms, both before and after cochlear implantation. On factor Openness to experience, the mean score was significantly lower before cochlear implantation, and remained so thereafter. Openness to experience may be reduced in some groups of deaf or hard of hearing persons. Cochlear implantation had no effect on any personality factor, at least not after two years of implant use.

Cognitive Screening of Adults With Postlingual Hearing Loss: A Systematic Review.

To systematically review the evidence for the use of cognitive screening tools for adults with postlingual hearing loss. PubMed, Embase, Scopus, PsycINFO (EBSCO), CINAHL (EBSCO), and CENTRAL (Cochrane Library) electronic databases were searched from inception until October 4, 2018. Articles were reviewed for inclusion by 2 independent reviewers. The references of included articles were hand-searched for additional relevant articles. Data were extracted by 2 independent extractors. Of 2092 articles imported from the search, 81 were included for the review. Nearly a third (31%, n = 25) included patients with profound hearing loss. In total, 23 unique tools were used for 105 unique applications. The Mini Mental Status Exam (MMSE) was the most commonly used (54%, n = 55), followed by the Montreal Cognitive Assessment (MoCA) (19%, n = 10). Nearly half of the tools were used to define patient inclusion or exclusion in a study (48%, n = 50), followed by examination of a change after an intervention (26%, n = 27). Two articles attempted to study the validity of the MMSE and MoCA for screening patients with mild to moderate hearing loss and found mixed effects of the auditory components. There were no validation studies identified from the search. Many different cognitive screening tools have been used to study patients with postlingual hearing loss. The effects of the auditory components of these tools may be deleterious but ultimately remain unclear from the available evidence. To date, there has been no validation of any cognitive screening tool to be used for adults with postlingual hearing loss.

Cochlear implantation outcomes in adults: A scoping review.

Cochlear implantation has become known as “the treatment of choice” for adults with severe to profound hearing loss. Wide variability exists, however, in the way hearing loss severity is measured and in the candidacy criteria used to recommend cochlear implantation.ObjectivesThis study aimed to provide a descriptive analysis of recent evidence available in the literature in relation to the efficacy of unilateral cochlear implantation in adults, the general findings of these studies, and the populations to which these findings apply. It also aimed to appraise the individual success rate and the magnitude of benefit following implantation.DesignA scoping review was conducted to identify English-language, peer-reviewed journal articles published between 2000 and 2018 assessing the outcomes of cochlear implantation in adults who received their first cochlear implant from 2000 onwards. To be included, studies had to report speech perception or self-reported measures of listening or quality of life at least three months after implantation. Systematic searches were conducted in Medline, Embase, Web of Science and Google Scholar. A two-stage screening approach was used, with seven reviewers independently screening titles and abstracts against inclusion criteria and three from this group further reviewing full-texts. A data charting form was developed and trialled, with 10% of the study data extracted in duplicate to compare results and further refine the form. Data relevant for efficacy analyses were extracted from studies with sample sizes of at least 10 participants.ResultsA total of 4182 abstracts were screened against inclusion criteria, and of these, 603 full-texts were further screened. After exclusion of non-eligible articles, 201 articles were included in the first part of this scoping review. The majority of these articles were case series or comparative studies without a concurrent group, and had small sample sizes. Data synthesis conducted with the 102 articles with more than 10 participants highlighted that the average word perception ability improved from 8.2% to 53.9% after implantation. Self-reported benefit improved by 21.5 percentage points. At the individual level, 82.0% of adults with postlingual hearing loss and 53.4% of adults with prelingual hearing loss improved their speech perception ability by 15 percentage points or more. A small proportion had poorer ability after implantation or had stopped using the cochlear implant.ConclusionsDespite broad inconsistencies in measurement, research design, and reporting across articles, it is evident that cochlear implantation is beneficial to the majority of adults of any age who have limited aided speech perception abilities. While many adults with severe-to-profound hearing loss may also have poor speech perception abilities with hearing aids, the validity of using hearing loss severity as a criterion for cochlear implantation has not been demonstrated. Clinical and research recommendations derived from this review are provided.

A rare genomic duplication in 2p14 underlies autosomal dominant hearing loss DFNA58.

Here we define a ~200Kb genomic duplication in 2p14 as the genetic signature that segregates with postlingual progressive sensorineural autosomal dominant hearing loss (HL) in 20 affected individuals from the DFNA58 family, first reported in 2009. The duplication includes two entire genes, PLEK and CNRIP1, and the first exon of PPP3R1 (protein coding), in addition to four uncharacterized long non-coding (lnc) RNA genes and part of a novel protein-coding gene. Quantitative analysis of mRNA expression in blood samples revealed selective overexpression of CNRIP1 and of two lncRNA genes (LOC107985892 and LOC102724389) in all affected members tested, but not in unaffected ones. Qualitative analysis of mRNA expression identified also fusion transcripts involving parts of PPP3R1, CNRIP1 and an intergenic region between PLEK and CNRIP1, in the blood of all carriers of the duplication, but were heterogeneous in nature. By in situ hybridization and immunofluorescence, we showed that Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea including the spiral ganglion neurons, suggesting changes in expression levels of these genes in the hearing organ could underlie the DFNA58 form of deafness. Our study highlights the value of studying rare genomic events leading to HL, such as copy number variations. Further studies will be required to determine which of these genes, either coding proteins or non-coding RNAs, is or are responsible for DFNA58 HL.

Event-Related Potential Evidence of Enhanced Visual Processing in Auditory-Associated Cortex in Adults with Hearing Loss

Objective: The present study investigated the characteristics of visual processing in the auditory-associated cortex in adults with hearing loss using event-related potentials. Methods: Ten subjects with bilateral postlingual hearing loss were recruited. Ten age- and sex-matched normal-hearing subjects were included as controls. Visual (“sound” and “non-sound” photos)-evoked potentials were performed. The P170 response in the occipital area as well as N1 and N2 responses in FC3 and FC4 were analyzed. Results: Adults with hearing loss had higher P170 amplitudes, significantly higher N2 amplitudes, and shorter N2 latency in response to “sound” and “non-sound” photo stimuli at both FC3 and FC4, with the exception of the N2 amplitude which responded to “sound” photo stimuli at FC3. Further topographic mapping analysis revealed that patients had a large difference in response to “sound” and “non-sound” photos in the right frontotemporal area, starting from approximately 200 to 400 ms. Localization of source showed the difference to be located in the middle frontal gyrus region (BA10) at around 266 ms. Conclusions: The significantly stronger responses to visual stimuli indicate enhanced visual processing in the auditory-associated cortex in adults with hearing loss, which may be attributed to cortical visual reorganization involving the right frontotemporal cortex.

Making the Case for Research on Disease-Modifying Treatments to Tackle Post-lingual Progressive Sensorineural Hearing Loss.

Hearing loss not only has a significant impact on the quality of life of patients and society, but its correlation with cognitive decline in an aging population will also increase the risk of incident dementia. While current management of hearing loss is focused on hearing rehabilitation (and essentially symptomatic), patients are suffering from the burden of progressive hearing loss before hearing aids or cochlear implants are fitted. Although these devices have a significant effect on speech understanding, they do not always lead to normal speech understanding, especially in noisy environments. A significant number of patients suffer from autosomal dominantly inherited disorders that can produce progressive sensorineural hearing loss. This includes DFNA9, a disorder caused by pathologic variants in the COCH gene that leads to post-lingual profound sensorineural hearing loss and bilateral vestibulopathy. Carriers of a pathogenic variant leading to DFNA9 can be diagnosed at the pre-symptomatic or early symptomatic stage which creates a window of opportunity for treatment. Preventing hearing loss from occurring or stabilizing progression would provide the opportunity to avoid hearing aids or cochlear implants and would be able to reduce the increased incidence of dementia. While innovative therapies for restoration of hearing have been studied for restoration of hearing in case of severe-to-profound sensorineural hearing loss and congenital hearing loss, further research is needed to study how we can modify disease progression in late-onset autosomal dominant hereditary sensorineural hearing loss. Recently, gene editing strategies have been explored in autosomal dominant disorders to disrupt dominant mutations selectively without affecting wild-type alleles.

Post-lingual non-syndromic hearing loss phenotype: a polygenic case with 2 biallelic mutations in MYO15A and MITF

BackgroundHearing loss (HL) represents the most common congenital sensory impairment with an incidence of 1–5 per 1000 live births. Non-syndromic hearing loss (NSHL) is an isolated finding that is not part of any other disorder accounting for 70% of all genetic hearing loss cases.MethodsIn the current study, we reported a polygenic mode of inheritance in an NSHL consanguineous family using exome sequencing technology and we evaluated the possible effect of the detected single nucleotide variants (SNVs) using in silico methods.ResultsTwo bi-allelic SNVs were detected in the affected patients; a MYO15A (. p.V485A) variant, and a novel MITF (p.P338L) variant. Along with these homozygous mutations, we detected two heterozygous variants in well described hearing loss genes (MYO7A and MYH14). The novel MITF p. Pro338Leu missense mutation was predicted to change the protein structure and function.ConclusionA novel MITF mutation along with a previously described MYO15A mutation segregate with an autosomal recessive non-syndromic HL case with a post-lingual onset. The findings highlight the importance of carrying whole exome sequencing for a comprehensive assessment of HL genetic heterogeneity.