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Iranian Journal of Public Health Feb 2024Hearing loss is the second most common disease after mental retardation in Iran. Autosomal recessive non-syndromic hearing loss (ARNSHL) is an extreme and highly...
BACKGROUND
Hearing loss is the second most common disease after mental retardation in Iran. Autosomal recessive non-syndromic hearing loss (ARNSHL) is an extreme and highly heterogeneous disease, for which more than 70 genes have been identified. Considering the frequency of family marriage as well as the importance of ARNSHL in Iran, we evaluated the genetic factors involved in this type of deafness.
METHODS
We performed the whole exome sequencing (WES) of eight Iranian subjects with severe nonsyndromic hearing loss selected from 110 well-characterized subjects with non-syndromic hearing loss from 2017-2019. The patients with mutated and genes were excluded from the study.
RESULTS
The use of the whole exome sequencing method revealed 10 different mutations in 7 genes, including c.1234G>T), (c.45DelC, c.466T>C), (c.12528-2A>C, c.16226-16227insAGTC), (c.7454delG), (c.3570+2T>C), (c.992G>A), (c.2359G>T, c.2353A>C). Seven new variants were observed in seven families including (c.1234G>T), (c.45DelC), (c.12528-2A>C), (c.7454delG), (c.16226-16227insAGTC), (c.3570+2T>C).
CONCLUSION
The causal mutation of ARNSHL was found in all patients using the WES. Meta-analysis studies can help to identify common mutations causing deafness in any population to facilitate identification of carriers and subjects with deafness.
PubMed: 38894825
DOI: 10.18502/ijph.v53i2.14930 -
Cancers May 2024NF2-related Schwannomatosis (NF2-SWN) is a disease that needs new solutions. The hallmark of NF2-SWN, a dominantly inherited neoplasia syndrome, is bilateral vestibular...
NF2-related Schwannomatosis (NF2-SWN) is a disease that needs new solutions. The hallmark of NF2-SWN, a dominantly inherited neoplasia syndrome, is bilateral vestibular schwannomas (VSs), which progressively enlarge, leading to sensorineural hearing loss, tinnitus, facial weakness, and pain that translates to social impairment and clinical depression. Standard treatments for growing VSs include surgery and radiation therapy (RT); however, both carry the risk of further nerve damage that can result in deafness and facial palsy. The resultant suffering and debility, in combination with the paucity of therapeutic options, make the effective treatment of NF2-SWN a major unmet medical need. A better understanding of these mechanisms is essential to developing novel therapeutic targets to control tumor growth and improve patients' quality of life. Previously, we developed the first orthotopic cerebellopontine angle mouse model of VSs, which faithfully mimics tumor-induced hearing loss. In this model, we observed that mice exhibit symptoms of ataxia and vestibular dysfunction. Therefore, we further developed a panel of five tests suitable for the mouse VS model and investigated how tumor growth and treatment affect gait, coordination, and motor function. Using this panel of ataxia tests, we demonstrated that both ataxia and motor function deteriorated concomitantly with tumor progression. We further demonstrated that (i) treatment with anti-VEGF resulted in tumor size reduction, mitigated ataxia, and improved rotarod performance; (ii) treatment with crizotinib stabilized tumor growth and led to improvements in both ataxia and rotarod performance; and (iii) treatment with losartan did not impact tumor growth nor ameliorate ataxia or motor function. Our studies demonstrated that these methods, paired with hearing tests, enable a comprehensive evaluation of tumor-induced neurological deficits and facilitate the assessment of the effectiveness of novel therapeutics to improve NF2 treatments.
PubMed: 38893082
DOI: 10.3390/cancers16111961 -
Journal of Clinical Medicine May 2024: To examine the surgical, audiological and patient-reported outcomes of the Osia 2 implant. : Data from 14 consecutive subjects undergoing implantation between April...
: To examine the surgical, audiological and patient-reported outcomes of the Osia 2 implant. : Data from 14 consecutive subjects undergoing implantation between April 2022 and November 2023 were reviewed. Ten subjects had conductive hearing loss, three had mixed hearing loss and one had single-sided deafness (SSD). Warble tone thresholds, Pure Tone Average (PTA) and Speech Discrimination Score (SDS) in quiet and in noise were determined unaided and aided. The subjective outcome was determined from two standardized questionnaires: (1) International Outcome Inventory for Hearing Aids (IOI-HA) and (2) Speech, Spatial and Qualities of Hearing Scale 12 (SSQ12b). : Unexpected postoperative pain was found in four cases. The warble tone thresholds exhibited a consistent reduction across all frequencies, contributing to a mean decrease of 27 dB in the aided PTA. SDS demonstrated notable improvements, with a 57.3% increase at 50 dB and a 55.6% increase at 65 dB. In noise, SDS exhibited a 43.9% improvement. The mean IOI-HA Score was 3.8, and the mean overall score for SSQ12b was 6.6, with consistent findings across the subgroups. : The Osia device emerges as a promising recommendation for individuals with conductive or mixed hearing loss, possibly also for those with SSD. Its safety and efficacy profile aligns with the broader category of active transcutaneous devices, demonstrating a reduced risk of wound infection compared to percutaneous alternatives. Both audiological assessments and subjective evaluations revealed positive outcomes.
PubMed: 38892822
DOI: 10.3390/jcm13113111 -
Animals : An Open Access Journal From... May 2024The reported positive outcomes of animal-assisted services have led to an emerging interest in many different aspects of human-animal interactions. The influence of an...
The reported positive outcomes of animal-assisted services have led to an emerging interest in many different aspects of human-animal interactions. The influence of an assistance animal is thought to encompass several psychosocial domains in the life of a person with a significant health impairment. However, little is known about the mechanisms underlying the relationship between Hearing Dogs and their owners. A prospective study design using a written questionnaire method was utilized to survey 58 current and 23 prospective Australian Lions Hearing Dogs owners. The Pet Expectations Inventory (PEI) was used to investigate the anticipated role of Hearing Dogs in waitlisted persons with hearing loss/Deafness, whereas the Lexington Attachment to Pets Scale (LAPS) was completed by current owners to assess emotional attachment. The results revealed a high mean PEI score (M = 73.1, SD = 10.9, Mdn = 73.0, range: 55-91), with prospective owners strongly expecting the role of Hearing Dogs to include companionship/love and security. Furthermore, strong attachment features were evident in the owners' relationships with Hearing Dogs, as demonstrated by a high total LAPS score (M = 81.2, SD = 7.5, range: 63-91). Mean scores for statements within the "people substitution" category were highest (range = 3.6/4.00-3.9/4.00). In this demographically homogenous study cohort, it appeared that the high expectations of potential Hearing Dog owners for their animals to serve supportive roles beyond hearing assistance should be achievable, as evidenced by the strong attachment relationships displayed between Hearing Dogs and their owners.
PubMed: 38891573
DOI: 10.3390/ani14111527 -
Scientific Reports Jun 2024While the relationships between spectral resolution, temporal resolution, and speech recognition are well defined in adults with cochlear implants (CIs), they are not...
While the relationships between spectral resolution, temporal resolution, and speech recognition are well defined in adults with cochlear implants (CIs), they are not well defined for prelingually deafened children with CIs, for whom language development is ongoing. This cross-sectional study aimed to better characterize these relationships in a large cohort of prelingually deafened children with CIs (N = 47; mean age = 8.33 years) by comprehensively measuring spectral resolution thresholds (measured via spectral modulation detection), temporal resolution thresholds (measured via sinusoidal amplitude modulation detection), and speech recognition (measured via monosyllabic word recognition, vowel recognition, and sentence recognition in noise via both fixed signal-to-noise ratio (SNR) and adaptively varied SNR). Results indicated that neither spectral or temporal resolution were significantly correlated with speech recognition in quiet or noise for children with CIs. Both age and CI experience had a moderate effect on spectral resolution, with significant effects for spectral modulation detection at a modulation rate of 0.5 cyc/oct, suggesting spectral resolution may improve with maturation. Thus, it is possible we may see an emerging relationship between spectral resolution and speech perception over time for children with CIs. While further investigation into this relationship is warranted, these findings demonstrate the need for new investigations to uncover ways of improving spectral resolution for children with CIs.
Topics: Humans; Cochlear Implants; Speech Perception; Child; Male; Female; Cross-Sectional Studies; Deafness; Child, Preschool; Signal-To-Noise Ratio; Noise; Adolescent
PubMed: 38890428
DOI: 10.1038/s41598-024-63932-w -
Trends in Hearing 2024This multi-center study examined the safety and effectiveness of cochlear implantation of children between 9 and 11 months of age. The intended impact was to support...
This multi-center study examined the safety and effectiveness of cochlear implantation of children between 9 and 11 months of age. The intended impact was to support practice regarding candidacy assessment and prognostic counseling of pediatric cochlear implant candidates. Data in the clinical chart of children implanted at 9-11 months of age with Cochlear Ltd devices at five cochlear implant centers in the United States and Canada were included in analyses. The study included data from two cohorts implanted with one or two Nucleus devices during the periods of January 1, 2012-December 31, 2017 (Cohort 1, n = 83) or between January 1, 2018 and May 15, 2020 (Cohort 2, n = 50). Major adverse events (requiring another procedure/hospitalization) and minor adverse events (managed with medication alone or underwent an expected course of treatment that did not require surgery or hospitalization) out to 2 years post-implant were monitored and outcomes measured by audiometric thresholds and parent-reports on the IT-MAIS and LittlEARS questionnaires were collected. Results revealed 60 adverse events in 41 children and 227 ears implanted (26%) of which 14 major events occurred in 11 children; all were transitory and resolved. Improved hearing with cochlear implant use was shown in all outcome measures. Findings reveal that the procedure is safe for infants and that they show clear benefits of cochlear implantation including increased audibility and hearing development.
Topics: Humans; Infant; Cochlear Implantation; Male; Female; Cochlear Implants; Treatment Outcome; Canada; United States; Time Factors; Retrospective Studies; Auditory Threshold; Postoperative Complications
PubMed: 38887094
DOI: 10.1177/23312165241261480 -
Investigative Ophthalmology & Visual... Jun 2024We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene.
PURPOSE
We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene.
METHODS
Fifty-three patients (mean age, 33.6 ± 16.7 years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed.
RESULTS
At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9 dB; 9.0 ± 10.2 dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0 µm; 250.7 ± 63.3 µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6 µm; 2615.5 ± 2370.4 µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]).
CONCLUSIONS
Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.
Topics: Humans; Male; Female; Adult; Prospective Studies; Tomography, Optical Coherence; Visual Acuity; Middle Aged; Electroretinography; Myosin VIIa; Visual Fields; Young Adult; Adolescent; Usher Syndromes; Genetic Therapy; Child; Visual Field Tests; Europe; Fluorescein Angiography; Follow-Up Studies; Aged; Longitudinal Studies; Disease Progression; Myosins; Retina
PubMed: 38884554
DOI: 10.1167/iovs.65.6.25 -
Advanced Genetics (Hoboken, N.J.) Jun 2024The co-occurrence of sensorineural hearing loss and male infertility has been reported in several instances, suggesting potential shared genetic underpinnings. One such...
The co-occurrence of sensorineural hearing loss and male infertility has been reported in several instances, suggesting potential shared genetic underpinnings. One such example is the contiguous gene deletion of and genes, previously associated with deafness-infertility syndrome (DIS) in males. Fifteen males with both hearing loss and infertility from southern India after exclusion for the DIS contiguous gene deletion and the gene mutations are subjected to exome sequencing. This resolves the genetic etiology in four probands for both the phenotypes; In the remaining 11 probands, two each conclusively accounted for deafness and male infertility etiologies. Genetic heterogeneity is well reflected in both phenotypes. Four recessive () and one dominant () for the deafness; six recessive genes (, and ) for male infertility can be conclusively ascribed. and genes are implicated earlier only in mice models, while the gene is implicated in chronic destructive airway diseases due to primary ciliary dyskinesia. This study would be the first to document the role of these genes in the male infertility phenotype in humans. The result suggests that deafness and infertility are independent events and do not segregate together among the probands.
PubMed: 38884051
DOI: 10.1002/ggn2.202300206 -
Frontiers in Neurology 2024The pathogenesis of idiopathic sudden sensorineural hearing loss remains unclear, and no substantial breakthroughs have been achieved in its treatment. Therefore, we...
BACKGROUND
The pathogenesis of idiopathic sudden sensorineural hearing loss remains unclear, and no substantial breakthroughs have been achieved in its treatment. Therefore, we conducted this study with the aim to investigate the clinical features and prognostic factors of patients with idiopathic sudden sensorineural hearing loss and auditory nerve enhancement by using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) of the inner ear.
METHODS
We retrospectively analyzed the clinical data of adult patients, who experienced sudden unilateral deafness and were admitted to the Department of Otolaryngology, Shandong Provincial ENT Hospital, between December 2020 and July 2021. Patients were divided into an auditory nerve enhancement group and a normal inner ear group, according to 3D-FLAIR MRI findings. Differences in sex, age, side, disease course, underlying diseases, dizziness/vertigo, vestibular function, degree of deafness, hearing classification, and treatment efficacy were analyzed.
RESULTS
Of the 112 cases of sudden idiopathic deafness, 16.07% exhibited enhancement of the auditory nerve on inner-ear 3D-FLAIR MRI. Statistically significant differences in the degree and type of hearing loss were detected between the two groups ( < 0.05). The rates of abnormal results in the caloric, vestibular-evoked myogenic potential, and video head impulse tests were higher in the auditory nerve enhancement group. The cure rate (11.1%) in patients with auditory nerve enhancement was lower than that in patients with normal inner ear MRI findings (28.7%); however, the difference was not statistically significant.
CONCLUSION
Findings from 3D-FLAIR MRI scans of the inner ear indicated that patients with sudden deafness and auditory nerve enhancement experienced severe hearing loss, aggravated vestibular function injury, and a significantly decreased cure rate. Prompt treatment, ideally within 2 weeks of disease onset, can facilitate hearing recovery.
PubMed: 38882699
DOI: 10.3389/fneur.2024.1410516 -
Orphanet Journal of Rare Diseases Jun 2024Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous...
BACKGROUND
Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype-phenotype correlations of USH2A-related retinal dystrophies in Taiwan.
RESULTS
In our cohort, the mean age at first visit was 47.66 ± 13.54 years, and the mean age at symptom onset, which was referred to the onset of nyctalopia and/or visual field constriction, was 31.21 ± 15.24 years. Among the variants identified, 23 (50%) were missense, 10 (22%) were splicing variants, 8 (17%) were nonsense, and 5 (11%) were frameshift mutations. The most predominant variant was c.2802T>G, which accounted for 21% of patients, and was located in exon 13. Patients with truncated alleles had significantly earlier symptom onset and seemly poorer disease progression regarding visual acuity, ellipsoid zone line length, and hypofluorescent lesions in the macula than those who had the complete gene. However, the clinical presentation revealed similar progression between patients with and without the c.2802T>G variant. During long-term follow-up, the patients had different ellipsoid zone line progression rates and were almost evenly distributed in the fast, moderate, and slow progression subgroups. Although a younger onset age and a smaller baseline intact macular area was observed in the fast progression subgroup, the results showed no significant difference.
CONCLUSIONS
This is the first cohort study to provide detailed genetic and longitudinal clinical analyses of patients with USH2A-related retinal dystrophies in Taiwan. The mutated allele frequency in exon 13 was high in Taiwan due to the predominant c.2802T>G variant. Moreover, truncated variants greatly impacted disease progression and determined the length of therapeutic windows. These findings provide insight into the characteristics of candidates for future gene therapies.
Topics: Adult; Female; Humans; Male; Middle Aged; Young Adult; Exons; Extracellular Matrix Proteins; Prevalence; Retinal Dystrophies; Taiwan; Usher Syndromes
PubMed: 38879497
DOI: 10.1186/s13023-024-03238-2