Hearing Loss in Adults

Cunningham, Lisa L.; Tucci, Debara L.

doi:10.1056/nejmra1616601

Cited by 423 publications

(404 citation statements)

References 79 publications

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“…HL prevalence generally increases with age but with decreasing monogenetic contribution (Cunningham & Tucci, 2017). Most dominant HL forms are postlingual and therefore are more difficult to distinguish from genetic forms (Shearer, Hildebrand, & Smith, 1993).…”

Section: Dominant Hearing Lossmentioning

confidence: 99%

Expert Specification of the ACMG/AMP Variant Interpretation Guidelines for Genetic Hearing Loss

Oza

DiStefano

Hemphill

et al. 2018

Preprint

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(200 WORD LIMIT)Due to the high genetic heterogeneity of hearing loss, current clinical testing includes sequencing large numbers of genes, which often yields a significant number of novel variants.Therefore, the standardization of variant interpretation is crucial to provide consistent and accurate diagnoses. The Hearing Loss Variant Curation Expert Panel was created within the Clinical Genome Resource to provide expert guidance for standardized genomic interpretation in the context of hearing loss. As one of its major tasks, our Expert Panel has adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) standards and guidelines for the interpretation of sequence variants in hearing loss genes. Here, we provide a comprehensive illustration of the newly specified ACMG/AMP . CC-BY-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/313734 doi: bioRxiv preprint first posted online May. 8, 2018; hearing loss rules. Three rules remained unchanged, four rules were removed, and the remaining twenty-one rules were specified. Of the specified rules, four had general recommendations, seven were gene/disease considerations, seven had strength-level specifications, and three rules had both gene/disease and strength-level specifications. These rules were further validated and refined using a pilot set of 51 variants assessed by curators.These hearing loss-specific ACMG/AMP rules will help standardize variant interpretation, ultimately leading to better care for individuals with hearing loss.

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Section: Dominant Hearing Lossmentioning

confidence: 99%

Expert Specification of the ACMG/AMP Variant Interpretation Guidelines for Genetic Hearing Loss

Oza

DiStefano

Hemphill

et al. 2018

Preprint

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“…Moreover, the economic burden of this disease on society is growing . Approximately 50% of hearing loss is caused by genetic factors, and 70% of hereditary hearing loss is classified as non‐syndromic hearing loss, which is not associated with other diseases . Non‐syndromic hearing loss has four genetic patterns, namely autosomal dominant, autosomal recessive, X‐linked, and mitochondrial .…”

Section: Introductionmentioning

confidence: 99%

Novel TRRAP mutation causes autosomal dominant non‐syndromic hearing loss

Xia

et al. 2019

Clinical Genetics

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Hereditary non‐syndromic hearing loss is the most common inherited sensory defect in humans. More than 40 genes have been identified as causative genes for autosomal dominant non‐syndromic hearing loss (ADNSHL), but there are many other candidate genes that remain to be discovered. We aimed to identify the causative gene mutation for post‐lingual progressive ADNSHL in a Chinese family. Whole‐exome sequencing, bioinformatic analysis, and Sanger sequencing were used to verify the co‐segregation of a novel pathogenic variant (NM_ 001244580, c.511C>T, p.Arg171Cys) in the TRansformation/tRanscription domain‐Associated Protein gene associated with hearing loss in a three‐generation Chinese family with ADNSHL). Additionally, three more novel variants of transformation/transcription domain associated protein (TRRAP) were detected in 66 sporadic cases of hearing loss. Morpholino oligonucleotides knockdown and clustered regularly interspaced short palindromic repeats/Cas9 knockout zebrafish were constructed to validate the genetic findings. Knockdown or knockout of TRRAP resulted in significant defects in the inner ear of zebrafish, indicating that TRRAP plays an important role in inner ear development. In conclusion, TRRAP (NM_ 001244580, c.511C>T, p.Arg171Cys) co‐segregated with hearing loss in a Chinese family with ADNSHL, and TRRAP deficiency caused hearing disability in zebrafish, suggesting TRRAP is a gene associated with ADNSHL.

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“…Sensorineural hearing loss is the most common form of human hearing loss and it can be due to several different factors including genetic mutations, ototoxic compound exposure, aging, infectious diseases, or environmental stress, such as prolonged exposure to excessive noise (6,18). In general, all these different factors can induce damage to the mechanosensory hair cells in the organ of Corti or the stria vascularis and they can also impair the function of the spiral ganglion neurons or of the more proximal auditory structures (19). Because of the limited regenerative ability of mammals, hair cells cannot regenerate after damage and the resultant hearing loss is permanent.…”

Section: Introductionmentioning

confidence: 99%

“…Notably, no signal has been observed in other blood vessels or other cochlear structures such as the Organ of Corti(1). The stria vascularis is the portion of the inner ear responsible for the endolymph production, which is important for the metabolic support of the Organ of Corti (1,19). Therefore, it has been postulated that, in those specific structures, AK2 could work as an ecto-enzyme, controlling the ATP and/or potassium concentrations in the endolymph(1).…”

Section: Introductionmentioning

confidence: 99%

A model for reticular dysgenesis shows impaired sensory organ development and hair cell regeneration linked to cellular stress

Rissone

Jimenez

Bishop

et al. 2019

Preprint

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Mutations in the gene AK2 are responsible for Reticular Dysgenesis (RD), a rare and severe form of primary immunodeficiency in children. RD patients have a severely shortened life expectancy and without treatment die a few weeks after birth. The only available therapeutic option for RD is bone marrow transplantation. To gain insight into the pathophysiology of RD, we previously created zebrafish models for an AK2 deficiency. One of the clinical features of RD is hearing loss, but its pathology and causes have not been determined. In adult mammals, sensory hair cells of the inner ear do not regenerate; however, their regeneration has been observed in several nonmammalian vertebrates, including zebrafish. Therefore, we use our RD zebrafish models to determine if AK2 deficiency affects sensory organ development and/or hair cell regeneration. Our studies indicated that AK2 is required for the correct development, survival and regeneration of sensory hair cells. Interestingly, AK2 deficiency induces the expression of several oxidative stress markers and it triggers an increased level of cell death in the hair cells. Finally, we show that glutathione treatment can partially rescue hair cell development in the sensory organs in our RD models, pointing to the potential use of antioxidants as a supportive therapeutic modality for RD patients, not only to increase their chances of survival, but to prevent or ameliorate their sensorineural hearing deficits.

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Hearing Loss in Adults

Cited by 423 publications

References 79 publications

Expert Specification of the ACMG/AMP Variant Interpretation Guidelines for Genetic Hearing Loss

Expert Specification of the ACMG/AMP Variant Interpretation Guidelines for Genetic Hearing Loss

Novel TRRAP mutation causes autosomal dominant non‐syndromic hearing loss

A model for reticular dysgenesis shows impaired sensory organ development and hair cell regeneration linked to cellular stress

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