Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.2
2.8
Journals
Genes
Special Issues
Genetics of Ear Development and Hearing Loss
share announcement

Genetics of Ear Development and Hearing Loss

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 8553

Special Issue Editor

Prof. Dr. Rick A. Friedman

E-Mail Website
Guest Editor
School of Medicine, University of California San Diego, La Jolla, CA 92037, USA
Interests: genetics of common forms of hearing loss; GWAS; age-related hearing loss; noise-induced hearing loss

Special Issue Information

Dear Colleagues,

It is with great pleasure that I am undertaking this role as Guest Editor for a Special Issue dedicated to the very important and rapidly accelerating field of the genetic underpinnings of ear development and hearing loss. Over the past several decades, there have been many significant advancements in our field, facilitating genetic discovery in both humans and mice.  Whole genome genotyping, sequencing, and whole exome sequencing are permitting scientists to characterize and discover the genes and pathways so critical to normal hearing and balance.  Gene editing has facilitated the rapid development of discovery in model systems including whole animal stem cells. The rapid development of tools for studying the tertiary structure of the mammalian genome combined with single-cell RNA seq has led to the characterization of the complexities of gene expression and regulation. In this Special Issue, we hope to provide the current state of the art in auditory genetics and end with a look toward the future of directed therapies.

Prof. Dr. Rick A. Friedman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hearing loss
  • auditory genetics
  • genome sequencing
  • whole exome sequencing

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

13 pages, 957 KiB  
Article
The Genetic Background of Hearing Loss in Patients with EVA and Cochlear Malformation
by Natalia Bałdyga, Dominika Oziębło, Nina Gan, Mariusz Furmanek, Marcin L. Leja, Henryk Skarżyński and Monika Ołdak
Genes 2023, 14(2), 335; https://doi.org/10.3390/genes14020335 - 28 Jan 2023
Cited by 1 | Viewed by 1911
Abstract
The most frequently observed congenital inner ear malformation is enlarged vestibular aqueduct (EVA). It is often accompanied with incomplete partition type 2 (IP2) of the cochlea and a dilated vestibule, which together constitute Mondini malformation. Pathogenic SLC26A4 variants are considered the major cause [...] Read more.
The most frequently observed congenital inner ear malformation is enlarged vestibular aqueduct (EVA). It is often accompanied with incomplete partition type 2 (IP2) of the cochlea and a dilated vestibule, which together constitute Mondini malformation. Pathogenic SLC26A4 variants are considered the major cause of inner ear malformation but the genetics still needs clarification. The aim of this study was to identify the cause of EVA in patients with hearing loss (HL). Genomic DNA was isolated from HL patients with radiologically confirmed bilateral EVA (n = 23) and analyzed by next generation sequencing using a custom HL gene panel encompassing 237 HL-related genes or a clinical exome. The presence and segregation of selected variants and the CEVA haplotype (in the 5′ region of SLC26A4) was verified by Sanger sequencing. Minigene assay was used to evaluate the impact of novel synonymous variant on splicing. Genetic testing identified the cause of EVA in 17/23 individuals (74%). Two pathogenic variants in the SLC26A4 gene were identified as the cause of EVA in 8 of them (35%), and a CEVA haplotype was regarded as the cause of EVA in 6 of 7 patients (86%) who carried only one SLC26A4 genetic variant. In two individuals with a phenotype matching branchio-oto-renal (BOR) spectrum disorder, cochlear hypoplasia resulted from EYA1 pathogenic variants. In one patient, a novel variant in CHD7 was detected. Our study shows that SLC26A4, together with the CEVA haplotype, accounts for more than half of EVA cases. Syndromic forms of HL should also be considered in patients with EVA. We conclude that to better understand inner ear development and the pathogenesis of its malformations, there is a need to look for pathogenic variants in noncoding regions of known HL genes or to link them with novel candidate HL genes. Full article
(This article belongs to the Special Issue Genetics of Ear Development and Hearing Loss)
►▼ Show Figures

Figure 1

15 pages, 629 KiB  
Article
Negative Molecular Diagnostics in Non-Syndromic Hearing Loss: What Next?
by Thomas Clabout, Laurence Maes, Frederic Acke, Wim Wuyts, Kristof Van Schil, Paul Coucke, Sandra Janssens and Els De Leenheer
Genes 2023, 14(1), 105; https://doi.org/10.3390/genes14010105 - 29 Dec 2022
Cited by 3 | Viewed by 2105
Abstract
Congenital hearing loss has an impact on almost every facet of life. In more than 50% of cases, a genetic cause can be identified. Currently, extensive genetic testing is available, although the etiology of some patients with obvious familial hearing loss remains unknown. [...] Read more.
Congenital hearing loss has an impact on almost every facet of life. In more than 50% of cases, a genetic cause can be identified. Currently, extensive genetic testing is available, although the etiology of some patients with obvious familial hearing loss remains unknown. We selected a cohort of mutation-negative patients to optimize the diagnostic yield for genetic hearing impairment. In this retrospective study, 21 patients (17 families) with negative molecular diagnostics for non-syndromic hearing loss (gene panel analysis) were included based on a positive family history with a similar type of hearing loss. Additional genetic testing was performed using a whole exome sequencing panel (WESHL panel v2.0) in four families with the strongest likelihood of genetic hearing impairment. In this cohort (n = 21), the severity of hearing loss was most commonly moderate (52%). Additional genetic testing revealed pathogenic copy number variants in the STRC gene in two families. In summary, regular re-evaluation of hearing loss patients with presumably genetic etiology after negative molecular diagnostics is recommended, as we might miss newly discovered deafness genes. The switch from gene panel analysis to whole exome sequencing or whole genome sequencing for the testing of congenital hearing loss seems promising. Full article
(This article belongs to the Special Issue Genetics of Ear Development and Hearing Loss)
►▼ Show Figures

Figure 1

17 pages, 6870 KiB  
Article
Mitochondrial tRNAGln 4394C>T Mutation May Contribute to the Clinical Expression of 1555A>G-Induced Deafness
by Yu Ding, Yaoshu Teng, Qinxian Guo and Jianhang Leng
Genes 2022, 13(10), 1794; https://doi.org/10.3390/genes13101794 - 5 Oct 2022
Cited by 3 | Viewed by 1826
Abstract
The mitochondrial 1555A>G mutation plays a critical role in aminoglycoside-induced and non-syndromic hearing loss (AINSHL). Previous studies have suggested that mitochondrial secondary variants may modulate the clinical expression of m.1555A>G-induced deafness, but the molecular mechanism has remained largely undetermined. In this study, we [...] Read more.
The mitochondrial 1555A>G mutation plays a critical role in aminoglycoside-induced and non-syndromic hearing loss (AINSHL). Previous studies have suggested that mitochondrial secondary variants may modulate the clinical expression of m.1555A>G-induced deafness, but the molecular mechanism has remained largely undetermined. In this study, we investigated the contribution of a deafness-associated tRNAGln 4394C>T mutation to the clinical expression of the m.1555A>G mutation. Interestingly, a three-generation family with both the m.1555A>G and m.4394C>T mutations exhibited a higher penetrance of hearing loss than another family harboring only the m.1555A>G mutation. At the molecular level, the m.4394C>T mutation resides within a very conserved nucleotide of tRNAGln, which forms a new base-pairing (7T-66A) and may affect tRNA structure and function. Using trans-mitochondrial cybrid cells derived from three subjects with both the m.1555A>G and m.4394C>T mutations, three patients with only the m.1555A>G mutation and three control subjects without these primary mutations, we observed that cells with both the m.1555A>G and m.4394C>T mutations exhibited more severely impaired mitochondrial functions than those with only the m.1555A>G mutation. Furthermore, a marked decrease in mitochondrial RNA transcripts and respiratory chain enzymes was observed in cells harboring both the m.1555A>G and m.4394C>T mutations. Thus, our data suggest that the m.4394C>T mutation may play a synergistic role in the m.1555A>G mutation, enhancing mitochondrial dysfunctions and contributing to a high penetrance of hearing loss in families with both mtDNA pathogenic mutations. Full article
(This article belongs to the Special Issue Genetics of Ear Development and Hearing Loss)
►▼ Show Figures

Figure 1

10 pages, 921 KiB  
Article
New Genetic Variants in CYP2B6 and SLC6A Support the Role of Oxidative Stress in Familial Ménière’s Disease
by Sini Skarp, Johanna Korvala, Jouko Kotimäki, Martti Sorri, Minna Männikkö and Elina Hietikko
Genes 2022, 13(6), 998; https://doi.org/10.3390/genes13060998 - 1 Jun 2022
Cited by 5 | Viewed by 2051
Abstract
The objective was to study the genetic etiology of Ménière’s disease (MD) using next-generation sequencing in three families with three cases of MD. Whole exome sequencing was used to identify rare genetic variants co-segregating with MD in Finnish families. In silico estimations and [...] Read more.
The objective was to study the genetic etiology of Ménière’s disease (MD) using next-generation sequencing in three families with three cases of MD. Whole exome sequencing was used to identify rare genetic variants co-segregating with MD in Finnish families. In silico estimations and population databases were used to estimate the frequency and pathogenicity of the variants. Variants were validated and genotyped from additional family members using capillary sequencing. A geneMANIA analysis was conducted to investigate the functional pathways and protein interactions of candidate genes. Seven rare variants were identified to co-segregate with MD in the three families: one variant in the CYP2B6 gene in family I, one variant in GUSB and EPB42 in family II, and one variant in each of the SLC6A, ASPM, KNTC1, and OVCH1 genes in family III. Four of these genes were linked to the same co-expression network with previous familial MD candidate genes. Dysfunction of CYP2B6 and SLC6A could predispose to MD via the oxidative stress pathway. Identification of ASPM and KNTC1 as candidate genes for MD suggests dysregulation of mitotic spindle formation in familial MD. The genetic etiology of familial MD is heterogenic. Our findings suggest a role for genes acting on oxidative stress and mitotic spindle formation in MD but also highlight the genetic complexity of MD. Full article
(This article belongs to the Special Issue Genetics of Ear Development and Hearing Loss)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop