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Genetics in Medicine : Official Journal... Sep 2022Genes associated with nonsyndromic hearing loss are commonly included in reproductive carrier screening panels, which are now routinely offered in preconception and... (Review)
Review
PURPOSE
Genes associated with nonsyndromic hearing loss are commonly included in reproductive carrier screening panels, which are now routinely offered in preconception and prenatal care in many countries. However, there is debate whether hearing loss should be considered a medical condition appropriate for screening. This systematic review assessed research on opinions of those with a lived experience of deafness and the general public regarding genetic testing for deafness in the reproductive setting.
METHODS
Search of 5 online databases yielded 423 articles, 20 of which met inclusion criteria. We assessed the quality of each study, extracted data, and performed thematic analysis on qualitative studies.
RESULTS
Most studies indicated interest in the use of prenatal diagnosis for deafness. However, there were mixed views, and sometimes strongly held views, expressed regarding the reproductive options that should be available to those with an increased chance of having a child with deafness. Studies were small, from a limited number of countries, and most were too old to include views regarding preimplantation genetic testing.
CONCLUSION
There is a broad range of views regarding the use of reproductive options for deafness. Further research is essential to explore the benefits and harms of including nonsyndromic hearing loss genes in carrier screening.
Topics: Child; Deafness; Female; Genetic Testing; Humans; Pregnancy; Prenatal Diagnosis; Reproduction
PubMed: 35659827
DOI: 10.1016/j.gim.2022.05.005 -
Molecular Therapy : the Journal of the... Sep 2023Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor...
Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3 homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. A single AAV2-hTMPRSS3 injection in Tmprss3 mice of an average age of 18.5 months leads to sustained rescue of the auditory function to a level similar to wild-type mice. AAV2-hTMPRSS3 delivery rescues the hair cells and the spiral ganglions neurons. This study demonstrates successful gene therapy in an aged mouse model of human genetic deafness. It lays the foundation to develop AAV2-hTMPRSS3 gene therapy to treat DFNB8 patients, as a standalone therapy or in combination with cochlear implantation.
Topics: Adult; Humans; Mice; Animals; Infant; Serine Endopeptidases; Membrane Proteins; Hearing; Deafness; Genetic Therapy; Neoplasm Proteins
PubMed: 37244253
DOI: 10.1016/j.ymthe.2023.05.005 -
Human Genetics Apr 2022Since the 1990s, the study of inherited hearing disorders, mostly those detected at birth, in the prelingual period or in young adults, has led to the identification of... (Review)
Review
Since the 1990s, the study of inherited hearing disorders, mostly those detected at birth, in the prelingual period or in young adults, has led to the identification of their causal genes. The genes responsible for more than 140 isolated (non-syndromic) and about 400 syndromic forms of deafness have already been discovered. Studies of mouse models of these monogenic forms of deafness have provided considerable insight into the molecular mechanisms of hearing, particularly those involved in the development and/or physiology of the auditory sensory organ, the cochlea. In parallel, studies of these models have also made it possible to decipher the pathophysiological mechanisms underlying hearing impairment. This has led a number of laboratories to investigate the potential of gene therapy for curing these forms of deafness. Proof-of-concept has now been obtained for the treatment of several forms of deafness in mouse models, paving the way for clinical trials of cochlear gene therapy in patients in the near future. Nevertheless, peripheral deafness may also be associated with central auditory dysfunctions and may extend well beyond the auditory system itself, as a consequence of alterations to the encoded sensory inputs or involvement of the causal deafness genes in the development and/or functioning of central auditory circuits. Investigating the diversity, causes and underlying mechanisms of these central dysfunctions, the ways in which they could impede the expected benefits of hearing restoration by peripheral gene therapy, and determining how these problems could be remedied is becoming a research field in its own right. Here, we provide an overview of the current knowledge about the central deficits associated with genetic forms of deafness.
Topics: Animals; Cochlea; Deafness; Disease Models, Animal; Hearing Loss; Hearing Tests; Humans; Mice
PubMed: 34435241
DOI: 10.1007/s00439-021-02339-3 -
Journal of Epidemiology Jan 2022Mumps deafness causes serious problems, and incidence data are needed to identify its disease burden. However, such data are limited, and the reported incidence is... (Observational Study)
Observational Study
BACKGROUND
Mumps deafness causes serious problems, and incidence data are needed to identify its disease burden. However, such data are limited, and the reported incidence is highly variable. Nationwide studies in Japan with a large age range are lacking.
METHODS
This was a retrospective observational investigation of the 2005-2017 mumps burden using employment-based health insurance claims data. Data were analyzed for 5,190,326 people aged 0-64 years to estimate the incidence of mumps deafness.
RESULTS
Of 68,112 patients with mumps (36,423 males; 31,689 females), 102 (48 males; 54 females) developed mumps deafness-an incidence of 15.0 per 10,000 patients (1 in 668 patients). Fifty-four (52.9%) patients had mumps deafness in childhood (0-15 years), and 48 (47.1%) had mumps deafness in adolescence and adulthood (16-64 years); most cases occurred in childhood, the peak period for mumps onset. The incidence of mumps deafness per 10,000 patients was 73.6 in adolescence and adulthood, 8.4 times higher than the incidence of 8.8 in childhood (P < 0.001). In childhood, the incidence of mumps deafness was 7.2 times higher among 6-15-year-olds (13.8; 95% CI, 10.2-18.2) than among 0-5-year-olds (1.9; 95% CI, 0.6-4.5), and this difference was statistically significant (P < 0.001). No sex difference was observed.
CONCLUSIONS
The incidence of mumps deafness per 10,000 patients aged 0-64 years was 15.0 (1 in 668 patients). A secondary risk of deafness following mumps virus infection was identified not only for children, but also for adolescents and adults.
Topics: Adolescent; Adult; Child; Child, Preschool; Deafness; Female; Humans; Incidence; Infant; Infant, Newborn; Insurance; Japan; Male; Middle Aged; Mumps; Young Adult
PubMed: 33100297
DOI: 10.2188/jea.JE20200233 -
British Dental Journal Dec 2020
Topics: Deafness; Hearing Loss; Humans
PubMed: 33311654
DOI: 10.1038/s41415-020-2458-x -
BMC Bioinformatics Feb 2023Sudden sensorineural hearing loss is a common and frequently occurring condition in otolaryngology. Existing studies have shown that sudden sensorineural hearing loss is...
Sudden sensorineural hearing loss is a common and frequently occurring condition in otolaryngology. Existing studies have shown that sudden sensorineural hearing loss is closely associated with mutations in genes for inherited deafness. To identify these genes associated with deafness, researchers have mostly used biological experiments, which are accurate but time-consuming and laborious. In this paper, we proposed a computational method based on machine learning to predict deafness-associated genes. The model is based on several basic backpropagation neural networks (BPNNs), which were cascaded as multiple-level BPNN models. The cascaded BPNN model showed a stronger ability for screening deafness-associated genes than the conventional BPNN. A total of 211 of 214 deafness-associated genes from the deafness variant database (DVD v9.0) were used as positive data, and 2110 genes extracted from chromosomes were used as negative data to train our model. The test achieved a mean AUC higher than 0.98. Furthermore, to illustrate the predictive performance of the model for suspected deafness-associated genes, we analyzed the remaining 17,711 genes in the human genome and screened the 20 genes with the highest scores as highly suspected deafness-associated genes. Among these 20 predicted genes, three genes were mentioned as deafness-associated genes in the literature. The analysis showed that our approach has the potential to screen out highly suspected deafness-associated genes from a large number of genes, and our predictions could be valuable for future research and discovery of deafness-associated genes.
Topics: Humans; Deafness; Hearing Loss, Sensorineural; Genetic Testing; Mutation; Neural Networks, Computer
PubMed: 36803022
DOI: 10.1186/s12859-023-05182-7 -
Vaccine Jan 2022COVID-19 has spread worldwide and is one of the most threatening infectious diseases in the world. Vaccination is known as an effective method to protect susceptible...
COVID-19 has spread worldwide and is one of the most threatening infectious diseases in the world. Vaccination is known as an effective method to protect susceptible populations against such diseases. The Coronavirus vaccine developed by Sinovac has been shown to have a high protective effect, but it also has potential adverse events. For example, our department saw two patients with reported cases of deafness that occurred after inoculation with the Sinovac Coronavirus vaccine. While deafness is only a rare adverse event from the Coronavirus vaccine, whether other vaccination centers, hospitals, and centers for disease control (CDCs) have encountered similar cases still needs to be investigated, reported, and analyzed.
Topics: COVID-19; COVID-19 Vaccines; Deafness; Humans; SARS-CoV-2; Vaccination
PubMed: 34895936
DOI: 10.1016/j.vaccine.2021.11.091 -
HNO Aug 2021This article presents a case of sudden bilateral deafness in the context of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and resultant...
This article presents a case of sudden bilateral deafness in the context of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and resultant coronavirus disease 2019 (COVID-19). After treatment in the intensive care unit for acute respiratory distress syndrome and acute kidney failure, hearing ability had drastically changed. While hearing had been subjectively normal before the infection, deafness was now measured on the left and profound hearing loss on the right ear. The patient was treated with cochlea implants on the left and a hearing aid in the right ear. The hearing loss is most likely a complication of COVID-19.
Topics: COVID-19; Cochlear Implantation; Cochlear Implants; Deafness; Hearing Loss, Sudden; Humans; RNA, Viral; SARS-CoV-2; Speech Perception
PubMed: 33837445
DOI: 10.1007/s00106-021-01040-1 -
BMC Medical Genomics Jan 2022Hearing loss (HL) is the most frequent sensory deficit in humans, HL has strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment...
BACKGROUND
Hearing loss (HL) is the most frequent sensory deficit in humans, HL has strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counseling for the patient's family.
METHODS
We undertook pedigree analysis in 92 Chinese non-syndromic HL patients by targeted next-generation sequencing and Sanger sequencing.
RESULTS
Among the 92 HL patients, 18 were assigned a molecular diagnosis with 33 different variants in 14 deafness genes. Eighteen of the variants in 12 deafness genes were novel. Variants in TMC1, CDH23, LOXHD1 and USH2A were each detected in two probands, and variants in POU3F4, OTOA, GPR98, GJB6, TRIOBP, SLC26A4, MYO15A, TNC, STRC and TMPRSS3 were each detected in one proband.
CONCLUSION
Our findings expand the spectrum of deafness gene variation, which will inform genetic diagnosis of deafness and add to the theoretical basis for the prevention of deafness.
Topics: Asian People; China; Deafness; High-Throughput Nucleotide Sequencing; Humans; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Mutation; Neoplasm Proteins; POU Domain Factors; Pedigree; Serine Endopeptidases; Usher Syndromes
PubMed: 35062939
DOI: 10.1186/s12920-022-01158-3 -
Pediatrics Jun 2022Infants with profound hearing loss are typically considered for cochlear implantation. Many insurance providers deny implantation to children with developmental...
BACKGROUND AND OBJECTIVES
Infants with profound hearing loss are typically considered for cochlear implantation. Many insurance providers deny implantation to children with developmental impairments because they have limited potential to acquire verbal communication. We took advantage of differing insurance coverage restrictions to compare outcomes after cochlear implantation or continued hearing aid use.
METHODS
Young children with deafness were identified prospectively from 2 different states, Texas and California, and followed longitudinally for an average of 2 years. Children in cohort 1 (n = 138) had normal cognition and adaptive behavior and underwent cochlear implantation. Children in cohorts 2 (n = 37) and 3 (n = 29) had low cognition and low adaptive behavior. Those in cohort 2 underwent cochlear implantation, whereas those in cohort 3 were treated with hearing aids.
RESULTS
Cohorts did not substantially differ in demographic characteristics. Using cohort 2 as the reference, children in cohort 1 showed more rapid gains in cognitive, adaptive function, language, and auditory skills (estimated coefficients, 0.166 to 0.403; P ≤ .001), whereas children in cohort 3 showed slower gains (-0.119 to -0.243; P ≤ .04). Children in cohort 3 also had greater increases in stress within the parent-child system (1.328; P = .02), whereas cohorts 1 and 2 were not different.
CONCLUSIONS
Cochlear implantation benefits children with deafness and developmental delays. This finding has health policy implications not only for private insurers but also for large, statewide, publicly administered programs. Cognitive and adaptive skills should not be used as a "litmus test" for pediatric cochlear implantation.
Topics: Child; Child, Preschool; Cochlear Implantation; Cochlear Implants; Deafness; Developmental Disabilities; Hearing Aids; Humans; Infant; Language Development; Speech Perception
PubMed: 35607935
DOI: 10.1542/peds.2021-055459