Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
3.7
4.7
Journals
Biomedicines
Special Issues
Genetic Research on Hearing Loss 2.0
share announcement

Genetic Research on Hearing Loss 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular Genetics and Genetic Diseases".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 11829

Special Issue Editor

Dr. Anna Morgan

E-Mail Website
Guest Editor
Institute for Maternal and Child Health—IRCCS, Burlo Garofolo, 34127 Trieste, Italy
Interests: hearing loss; age-related hearing loss; next-generation sequencing; whole exome sequencing; molecular diagnosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hearing loss (HL) is the most common sensory impairment worldwide. It is characterized by a high clinical/genetic heterogeneity with ~123 genes reported so far and more than 400 HL syndromes described. Genetic factors account for 50–60% of all the cases; however, despite the efforts made in recent years, many patients still lack a final molecular diagnosis.

This Special Issue aims to collect reviews and original articles on recent investigations of the molecular basis of hearing loss, both syndromic and non-syndromic, as well as age-related hearing loss. All manuscripts, both experimental and theoretical contributions, should highlight:

  • The molecular mechanisms at the level of single genes/proteins or their networks;
  • The benefit from the vast amounts of information that can be garnered from genetic work in this field;
  • New possible candidate genes for monogenic and complex forms of HL.

Dr. Anna Morgan
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. Biomedicines 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

  • genetics of hearing loss
  • genetics of age-related hearing loss
  • next-generation sequencing
  • new gene discovery
  • genotype–phenotype correlation

Published Papers (6 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

Jump to: Review

10 pages, 1296 KiB  
Article
Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects
by María Domínguez-Ruiz, Laura Ruiz-Palmero, Paula I. Buonfiglio, Irene García-Vaquero, Elena Gómez-Rosas, Marina Goñi, Manuela Villamar, Matías Morín, Miguel A. Moreno-Pelayo, Ana B. Elgoyhen, Francisco J. del Castillo, Viviana Dalamón and Ignacio del Castillo
Biomedicines 2023, 11(11), 2943; https://doi.org/10.3390/biomedicines11112943 - 31 Oct 2023
Viewed by 1263
Abstract
Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in GJB2, encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the STRC gene result [...] Read more.
Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in GJB2, encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the STRC gene result in the DFNB16 type of autosomal recessive NSHI, a common cause of moderate hearing loss. STRC is located in a tandem duplicated region that includes the STRCP1 pseudogene, and so it is prone to rearrangements causing structural variations. Firstly, we screened a cohort of 122 Spanish familial cases of non-DFNB1 NSHI with at least two affected siblings and unaffected parents, and with different degrees of hearing loss (mild to profound). Secondly, we screened a cohort of 64 Spanish sporadic non-DFNB1 cases, and a cohort of 35 Argentinean non-DFNB1 cases, all of them with moderate hearing loss. Amplification of marker D15S784, massively parallel DNA sequencing, multiplex ligation-dependent probe amplification and long-range gene-specific PCR followed by Sanger sequencing were used to search and confirm single-nucleotide variants (SNVs) and deletions involving STRC. Causative variants were found in 13 Spanish familial cases (10.7%), 5 Spanish simplex cases (7.8%) and 2 Argentinean cases (5.7%). In all, 34 deleted alleles and 6 SNVs, 5 of which are novel. All affected subjects had moderate hearing impairment. Our results further support this strong genotype–phenotype correlation and highlight the significant contribution of STRC mutations to moderate NSHI in the Spanish population. Full article
(This article belongs to the Special Issue Genetic Research on Hearing Loss 2.0)
►▼ Show Figures

Graphical abstract

14 pages, 2977 KiB  
Article
Combined Presence in Heterozygosis of Two Variant Usher Syndrome Genes in Two Siblings Affected by Isolated Profound Age-Related Hearing Loss
by Nica Borgese, Andrés Guillén-Samander, Sara Francesca Colombo, Giulia Mancassola, Federica Di Berardino, Diego Zanetti and Paola Carrera
Biomedicines 2023, 11(10), 2657; https://doi.org/10.3390/biomedicines11102657 - 28 Sep 2023
Viewed by 1054
Abstract
Sensorineural age-related hearing loss affects a large proportion of the elderly population, and has both environmental and genetic causes. Notwithstanding increasing interest in this debilitating condition, the genetic risk factors remain largely unknown. Here, we report the case of two sisters affected by [...] Read more.
Sensorineural age-related hearing loss affects a large proportion of the elderly population, and has both environmental and genetic causes. Notwithstanding increasing interest in this debilitating condition, the genetic risk factors remain largely unknown. Here, we report the case of two sisters affected by isolated profound sensorineural hearing loss after the age of seventy. Genomic DNA sequencing revealed that the siblings shared two monoallelic variants in two genes linked to Usher Syndrome (USH genes), a recessive disorder of the ear and the retina: a rare pathogenic truncating variant in USH1G and a previously unreported missense variant in ADGRV1. Structure predictions suggest a negative effect on protein stability of the latter variant, allowing its classification as likely pathogenic according to American College of Medical Genetics criteria. Thus, the presence in heterozygosis of two recessive alleles, which each cause syndromic deafness, may underlie digenic inheritance of the age-related non-syndromic hearing loss of the siblings, a hypothesis that is strengthened by the knowledge that the two genes are integrated in the same functional network, which underlies stereocilium development and organization. These results enlarge the spectrum and complexity of the phenotypic consequences of USH gene mutations beyond the simple Mendelian inheritance of classical Usher syndrome. Full article
(This article belongs to the Special Issue Genetic Research on Hearing Loss 2.0)
►▼ Show Figures

Figure 1

19 pages, 1042 KiB  
Article
The Enigmatic Genetic Landscape of Hereditary Hearing Loss: A Multistep Diagnostic Strategy in the Italian Population
by Beatrice Spedicati, Aurora Santin, Giuseppe Giovanni Nardone, Elisa Rubinato, Stefania Lenarduzzi, Claudio Graziano, Livia Garavelli, Sara Miccoli, Stefania Bigoni, Anna Morgan and Giorgia Girotto
Biomedicines 2023, 11(3), 703; https://doi.org/10.3390/biomedicines11030703 - 24 Feb 2023
Cited by 3 | Viewed by 1732
Abstract
Hearing loss is the most frequent sensorineural disorder, affecting approximately 1:1000 newborns. Hereditary forms (HHL) represent 50–60% of cases, highlighting the relevance of genetic testing in deaf patients. HHL is classified as non-syndromic (NSHL—70% of cases) or syndromic (SHL—30% of cases). In this [...] Read more.
Hearing loss is the most frequent sensorineural disorder, affecting approximately 1:1000 newborns. Hereditary forms (HHL) represent 50–60% of cases, highlighting the relevance of genetic testing in deaf patients. HHL is classified as non-syndromic (NSHL—70% of cases) or syndromic (SHL—30% of cases). In this study, a multistep and integrative approach aimed at identifying the molecular cause of HHL in 102 patients, whose GJB2 analysis already showed a negative result, is described. In NSHL patients, multiplex ligation probe amplification and long-range PCR analyses of the STRC gene solved 13 cases, while whole exome sequencing (WES) identified the genetic diagnosis in 26 additional ones, with a total detection rate of 47.6%. Concerning SHL, WES detected the molecular cause in 55% of cases. Peculiar findings are represented by the identification of four subjects displaying a dual molecular diagnosis and eight affected by non-syndromic mimics, five of them presenting Usher syndrome type 2. Overall, this study provides a detailed characterisation of the genetic causes of HHL in the Italian population. Furthermore, we highlighted the frequency of Usher syndrome type 2 carriers in the Italian population to pave the way for a more effective implementation of diagnostic and follow-up strategies for this disease. Full article
(This article belongs to the Special Issue Genetic Research on Hearing Loss 2.0)
►▼ Show Figures

Figure 1

Review

Jump to: Research

33 pages, 1073 KiB  
Review
Recent Therapeutic Progress and Future Perspectives for the Treatment of Hearing Loss
by Joey Lye, Derek S. Delaney, Fiona K. Leith, Varda S. Sardesai, Samuel McLenachan, Fred K. Chen, Marcus D. Atlas and Elaine Y. M. Wong
Biomedicines 2023, 11(12), 3347; https://doi.org/10.3390/biomedicines11123347 - 18 Dec 2023
Cited by 1 | Viewed by 1880
Abstract
Up to 1.5 billion people worldwide suffer from various forms of hearing loss, with an additional 1.1 billion people at risk from various insults such as increased consumption of recreational noise-emitting devices and ageing. The most common type of hearing impairment is sensorineural [...] Read more.
Up to 1.5 billion people worldwide suffer from various forms of hearing loss, with an additional 1.1 billion people at risk from various insults such as increased consumption of recreational noise-emitting devices and ageing. The most common type of hearing impairment is sensorineural hearing loss caused by the degeneration or malfunction of cochlear hair cells or spiral ganglion nerves in the inner ear. There is currently no cure for hearing loss. However, emerging frontier technologies such as gene, drug or cell-based therapies offer hope for an effective cure. In this review, we discuss the current therapeutic progress for the treatment of hearing loss. We describe and evaluate the major therapeutic approaches being applied to hearing loss and summarize the key trials and studies. Full article
(This article belongs to the Special Issue Genetic Research on Hearing Loss 2.0)
►▼ Show Figures

Figure 1

21 pages, 611 KiB  
Review
Clinical and Molecular Aspects Associated with Defects in the Transcription Factor POU3F4: A Review
by Emanuele Bernardinelli, Florian Huber, Sebastian Roesch and Silvia Dossena
Biomedicines 2023, 11(6), 1695; https://doi.org/10.3390/biomedicines11061695 - 12 Jun 2023
Cited by 2 | Viewed by 1461
Abstract
X-linked deafness (DFNX) is estimated to account for up to 2% of cases of hereditary hearing loss and occurs in both syndromic and non-syndromic forms. POU3F4 is the gene most commonly associated with X-linked deafness (DFNX2, DFN3) and accounts for about 50% of [...] Read more.
X-linked deafness (DFNX) is estimated to account for up to 2% of cases of hereditary hearing loss and occurs in both syndromic and non-syndromic forms. POU3F4 is the gene most commonly associated with X-linked deafness (DFNX2, DFN3) and accounts for about 50% of the cases of X-linked non-syndromic hearing loss. This gene codes for a transcription factor of the POU family that plays a major role in the development of the middle and inner ear. The clinical features of POU3F4-related hearing loss include a pathognomonic malformation of the inner ear defined as incomplete partition of the cochlea type 3 (IP-III). Often, a perilymphatic gusher is observed upon stapedectomy during surgery, possibly as a consequence of an incomplete separation of the cochlea from the internal auditory canal. Here we present an overview of the pathogenic gene variants of POU3F4 reported in the literature and discuss the associated clinical features, including hearing loss combined with additional phenotypes such as cognitive and motor developmental delays. Research on the transcriptional targets of POU3F4 in the ear and brain is in its early stages and is expected to greatly advance our understanding of the pathophysiology of POU3F4-linked hearing loss. Full article
(This article belongs to the Special Issue Genetic Research on Hearing Loss 2.0)
►▼ Show Figures

Figure 1

28 pages, 523 KiB  
Review
Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review
by Mirko Aldè, Giovanna Cantarella, Diego Zanetti, Lorenzo Pignataro, Ignazio La Mantia, Luigi Maiolino, Salvatore Ferlito, Paola Di Mauro, Salvatore Cocuzza, Jérôme René Lechien, Giannicola Iannella, Francois Simon and Antonino Maniaci
Biomedicines 2023, 11(6), 1616; https://doi.org/10.3390/biomedicines11061616 - 1 Jun 2023
Cited by 11 | Viewed by 3784
Abstract
Autosomal dominant non-syndromic hearing loss (HL) typically occurs when only one dominant allele within the disease gene is sufficient to express the phenotype. Therefore, most patients diagnosed with autosomal dominant non-syndromic HL have a hearing-impaired parent, although de novo mutations should be considered [...] Read more.
Autosomal dominant non-syndromic hearing loss (HL) typically occurs when only one dominant allele within the disease gene is sufficient to express the phenotype. Therefore, most patients diagnosed with autosomal dominant non-syndromic HL have a hearing-impaired parent, although de novo mutations should be considered in all cases of negative family history. To date, more than 50 genes and 80 loci have been identified for autosomal dominant non-syndromic HL. DFNA22 (MYO6 gene), DFNA8/12 (TECTA gene), DFNA20/26 (ACTG1 gene), DFNA6/14/38 (WFS1 gene), DFNA15 (POU4F3 gene), DFNA2A (KCNQ4 gene), and DFNA10 (EYA4 gene) are some of the most common forms of autosomal dominant non-syndromic HL. The characteristics of autosomal dominant non-syndromic HL are heterogenous. However, in most cases, HL tends to be bilateral, post-lingual in onset (childhood to early adulthood), high-frequency (sloping audiometric configuration), progressive, and variable in severity (mild to profound degree). DFNA1 (DIAPH1 gene) and DFNA6/14/38 (WFS1 gene) are the most common forms of autosomal dominant non-syndromic HL affecting low frequencies, while DFNA16 (unknown gene) is characterized by fluctuating HL. A long audiological follow-up is of paramount importance to identify hearing threshold deteriorations early and ensure prompt treatment with hearing aids or cochlear implants. Full article
(This article belongs to the Special Issue Genetic Research on Hearing Loss 2.0)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop