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Proceedings of the National Academy of... Mar 2019Autosomal recessive genetic forms (DFNB) account for most cases of profound congenital deafness. Adeno-associated virus (AAV)-based gene therapy is a promising...
Autosomal recessive genetic forms (DFNB) account for most cases of profound congenital deafness. Adeno-associated virus (AAV)-based gene therapy is a promising therapeutic option, but is limited by a potentially short therapeutic window and the constrained packaging capacity of the vector. We focus here on the otoferlin gene underlying DFNB9, one of the most frequent genetic forms of congenital deafness. We adopted a dual AAV approach using two different recombinant vectors, one containing the 5' and the other the 3' portions of otoferlin cDNA, which exceed the packaging capacity of the AAV when combined. A single delivery of the vector pair into the mature cochlea of mutant mice reconstituted the otoferlin cDNA coding sequence through recombination of the 5' and 3' cDNAs, leading to the durable restoration of otoferlin expression in transduced cells and a reversal of the deafness phenotype, raising hopes for future gene therapy trials in DFNB9 patients.
Topics: Animals; Deafness; Dependovirus; Disease Models, Animal; Genetic Therapy; Genetic Vectors; Humans; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic
PubMed: 30782832
DOI: 10.1073/pnas.1817537116 -
Frontiers in Endocrinology 2021To investigate the clinical features and mitochondrial mutations for maternally inherited diabetes and deafness. (Review)
Review
AIMS
To investigate the clinical features and mitochondrial mutations for maternally inherited diabetes and deafness.
METHODS
PubMed, Embase, Medline, Web of Science, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: "Maternally inherited diabetes and deafness" OR "MIDD" OR "Mitochondrial diabetes". The mutations and clinical features were analyzed. Correlation between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes was conducted by Spearman test. The significance level was set as p < 0.05. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows.
RESULTS
Totally 161 patients with 21 different mitochondrial mutations were enrolled. The most common mutation was the m.3243A>G mutation in 136 cases. Of 142 patients, 120 (84.51%) had family histories of diabetes or hearing loss. Hearing loss presented in 85.71% of the patients with mitochondrial mutations. Central nervous system diseases were found in 29.19%, myopathy in 22.98%, oculopathy in 23.60%, cardiac disease in 23.60%, and nephropathy in 13.66% of the patients. Forty-two of 101 (41.58%) patients were underweight. A significant negative correlation was found between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes.
CONCLUSIONS
The young onset of diabetes with low or normal BMI, maternal inheritance, and presence of impairments of multiple systems should prompt a genetic testing in order to differentiate MIDD from other types of diabetes earlier.
Topics: Biological Variation, Population; Cohort Studies; DNA, Mitochondrial; Deafness; Diabetes Mellitus, Type 2; Genetic Heterogeneity; Humans; Infant, Newborn; Mitochondrial Diseases; Mutation; Phenotype
PubMed: 34899594
DOI: 10.3389/fendo.2021.728043 -
European Journal of Human Genetics :... Jan 2022
Topics: Deafness; Humans; Pedigree
PubMed: 34819629
DOI: 10.1038/s41431-021-01006-5 -
Journal of the Association For Research... Feb 2023The cochlear implant (CI) is widely considered to be one of the most innovative and successful neuroprosthetic treatments developed to date. Although outcomes vary, CIs... (Review)
Review
The cochlear implant (CI) is widely considered to be one of the most innovative and successful neuroprosthetic treatments developed to date. Although outcomes vary, CIs are able to effectively improve hearing in nearly all recipients and can substantially improve speech understanding and quality of life for patients with significant hearing loss. A wealth of research has focused on underlying factors that contribute to success with a CI, and recent evidence suggests that the overall health of the cochlea could potentially play a larger role than previously recognized. This article defines and reviews attributes of cochlear health and describes procedures to evaluate cochlear health in humans and animal models in order to examine the effects of cochlear health on performance with a CI. Lastly, we describe how future biologic approaches can be used to preserve and/or enhance cochlear health in order to maximize performance for individual CI recipients.
Topics: Animals; Humans; Cochlear Implants; Quality of Life; Cochlear Implantation; Cochlea; Deafness
PubMed: 36600147
DOI: 10.1007/s10162-022-00882-y -
Audiology & Neuro-otology 2015
Topics: Adult; Child; Cochlear Implantation; Congresses as Topic; Deafness; Hearing Loss, Unilateral; Humans
PubMed: 25998566
DOI: 10.1159/000380740 -
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: 34019138
DOI: 10.1007/s00106-021-01041-0 -
Ugeskrift For Laeger Dec 2023The introduction of cochlear implants (CI) for pediatric populations with deafness has changed life conditions for deaf children markedly. A new generation of children... (Review)
Review
The introduction of cochlear implants (CI) for pediatric populations with deafness has changed life conditions for deaf children markedly. A new generation of children with CI has emerged, and this review investigates how it has been documented that early intervention with CI and enrolment in family-centered auditory-verbal intervention allow children to close the language gap and develop age-equivalent language before entering school. At the school level, children keep up the language level. Most importantly children assess themselves to have levels of social well-being comparable to their peers with normal hearing.
Topics: Child; Humans; Cochlear Implantation; Deafness; Cochlear Implants
PubMed: 38078473
DOI: No ID Found -
Human Genetics Apr 2022Sensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide... (Review)
Review
Sensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide significant benefit to many with SNHL, neither targets the cellular and molecular dysfunction that ultimately underlies SNHL. The successful development of more targeted approaches, such as growth factor, stem cell, and gene therapies, will require a yet deeper understanding of the underlying molecular mechanisms of human hearing and deafness. Unfortunately, the human inner ear cannot be biopsied without causing significant, irreversible damage to the hearing or balance organ. Thus, much of our current understanding of the cellular and molecular biology of human deafness, and of the human auditory system more broadly, has been inferred from observational and experimental studies in animal models, each of which has its own advantages and limitations. In 2013, researchers described a protocol for the generation of inner ear organoids from pluripotent stem cells (PSCs), which could serve as scalable, high-fidelity alternatives to animal models. Here, we discuss the advantages and limitations of conventional models of the human auditory system, describe the generation and characteristics of PSC-derived inner ear organoids, and discuss several strategies and recent attempts to model hereditary deafness in vitro. Finally, we suggest and discuss several focus areas for the further, intensive characterization of inner ear organoids and discuss the translational applications of these novel models of the human inner ear.
Topics: Deafness; Ear, Inner; Hearing Loss, Sensorineural; Hearing Tests; Humans; Organoids
PubMed: 34342719
DOI: 10.1007/s00439-021-02325-9 -
Annual Review of Genomics and Human... Aug 2022Current estimates suggest that nearly half a billion people worldwide are affected by hearing loss. Because of the major psychological, social, economic, and health... (Review)
Review
Current estimates suggest that nearly half a billion people worldwide are affected by hearing loss. Because of the major psychological, social, economic, and health ramifications, considerable efforts have been invested in identifying the genes and molecular pathways involved in hearing loss, whether genetic or environmental, to promote prevention, improve rehabilitation, and develop therapeutics. Genomic sequencing technologies have led to the discovery of genes associated with hearing loss. Studies of the transcriptome and epigenome of the inner ear have characterized key regulators and pathways involved in the development of the inner ear and have paved the way for their use in regenerative medicine. In parallel, the immense preclinical success of using viral vectors for gene delivery in animal models of hearing loss has motivated the industry to work on translating such approaches into the clinic. Here, we review the recent advances in the genomics of auditory function and dysfunction, from patient diagnostics to epigenetics and gene therapy.
Topics: Animals; Deafness; Ear, Inner; Genetic Therapy; Genomics; Hearing Loss; Humans
PubMed: 35667089
DOI: 10.1146/annurev-genom-121321-094136 -
Neural Plasticity 2016The effect of deafness on sensory abilities has been the topic of extensive investigation over the past decades. These investigations have mostly focused on visual... (Review)
Review
The effect of deafness on sensory abilities has been the topic of extensive investigation over the past decades. These investigations have mostly focused on visual capacities. We are only now starting to investigate how the deaf experience their own bodies and body-related abilities. Indeed, a growing corpus of research suggests that auditory input could play an important role in body-related processing. Deafness could therefore disturb such processes. It has also been suggested that many unexplained daily difficulties experienced by the deaf could be related to deficits in this underexplored field. In the present review, we propose an overview of the current state of knowledge on the effects of deafness on body-related processing.
Topics: Body Image; Deafness; Humans; Motor Activity; Neuronal Plasticity; Posture; Touch Perception
PubMed: 26881115
DOI: 10.1155/2016/5260671