gene therapy

Genetics and the Individualized Therapy of Vestibular Disorders

February 5, 2021

CATEGORY:
Research

SCREENSHOT:
Genetics and the Individualized Therapy of Vestibular Disorders

TITLE:
Genetics and the Individualized Therapy of Vestibular Disorders

CONTENT:
Front Neurol. 2021 Feb 5;12:633207. doi: 10.3389/fneur.2021.633207. eCollection 2021.

ABSTRACT

Background: Vestibular disorders (VDs) are a clinically divergent group of conditions that stem from pathology at the level of the inner ear, vestibulocochlear nerve, or central vestibular pathway. No etiology can be identified in the majority of patients with VDs. Relatively few families have been reported with VD, and so far, no causative genes have been identified despite the fact that more than 100 genes have been identified for inherited hearing loss. Inherited VDs, similar to deafness, are genetically heterogeneous and follow Mendelian inheritance patterns with all modes of transmission, as well as multifactorial inheritance. With advances in genetic sequencing, evidence of familial clustering in VD has begun to highlight the genetic causes of these disorders, potentially opening up new avenues of treatment, particularly in Meniere’s disease and disorders with comorbid hearing loss, such as Usher syndrome. In this review, we aim to present recent findings on the genetics of VDs, review the role of genetic sequencing tools, and explore the potential for individualized medicine in the treatment of these disorders. Methods: A search of the PubMed database was performed for English language studies relevant to the genetic basis of and therapies for vestibular disorders, using search terms including but not limited to: “genetics,” “genomics,” “vestibular disorders,” “hearing loss with vestibular dysfunction,” “individualized medicine,” “genome-wide association studies,” “precision medicine,” and “Meniere’s syndrome.” Results: Increasing numbers of studies on vestibular disorder genetics have been published in recent years. Next-generation sequencing and new genetic tools are being utilized to unearth the significance of the genomic findings in terms of understanding disease etiology and clinical utility, with growing research interest being shown for individualized gene therapy for some disorders. Conclusions: The genetic knowledge base for vestibular disorders is still in its infancy. Identifying the genetic causes of balance problems is imperative in our understanding of the biology of normal function of the vestibule and the disease etiology and process. There is an increasing effort to use new and efficient genetic sequencing tools to discover the genetic causes for these diseases, leading to the hope for precise and personalized treatment for these patients.

PMID:33613440 | PMC:PMC7892966 | DOI:10.3389/fneur.2021.633207

SOURCE:
Frontiers in neurology

PUBLISHER:

PMID:
pubmed:33613440

ID:
5dfa010a544eb3c21dde51db84c2481bpubmed:33613440

DOI:
10.3389/fneur.2021.633207

DATE – PUBLISHED:
Mon, 22 Feb 2021 06:00:00 -0500

DATE – DOI:
2021-02-05T18:51:58Z

DATE – ADDED:
03/07/21 02:55PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33613440/

LINK – DOI:
https://doi.org/10.3389/fneur.2021.633207

LINK – PUBLISHER:
https://www.frontiersin.org/articles/10.3389/fneur.2021.633207/full?utm_source=menierestreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-07T19:55:27+00:00, https://www.menierestreatmentreport.com.

OTOG as a Relevant Gene in Familial Meniere’s Disease: the groundwork for genetic testing in MD

April 2, 2020

https://journals.lww.com/ear-hearing/Abstract/9000/Burden_of_Rare_Variants_in_the_OTOG_Gene_in.98668.aspx

https://www.ncbi.nlm.nih.gov/pubmed/32251013?dopt=Abstract

Burden of Rare Variants in the OTOG Gene in Familial Meniere’s Disease.

Ear Hear. 2020 Apr 02;:

Authors: Roman-Naranjo P, Gallego-Martinez A, Soto-Varela A, Aran I, Moleon MDC, Espinosa-Sanchez JM, Amor-Dorado JC, Batuecas-Caletrio A, Perez-Vazquez P, Lopez-Escamez JA

Abstract

OBJECTIVES: Meniere’s disease (MD) is a rare inner ear disorder characterized by sensorineural hearing loss, episodic vertigo, and tinnitus. Familial MD has been reported in 6 to 9% of sporadic cases, and few genes including FAM136A, DTNA, PRKCB, SEMA3D, and DPT have been involved in single families, suggesting genetic heterogeneity. In this study, the authors recruited 46 families with MD to search for relevant candidate genes for hearing loss in familial MD.

DESIGN: Exome sequencing data from MD patients were analyzed to search for rare variants in hearing loss genes in a case-control study. A total of 109 patients with MD (73 familial cases and 36 early-onset sporadic patients) diagnosed according to the diagnostic criteria defined by the Barany Society were recruited in 11 hospitals. The allelic frequencies of rare variants in hearing loss genes were calculated in individuals with familial MD. A single rare variant analysis and a gene burden analysis (GBA) were conducted in the dataset selecting 1 patient from each family. Allelic frequencies from European and Spanish reference datasets were used as controls.

RESULTS: A total of 5136 single-nucleotide variants in hearing loss genes were considered for single rare variant analysis in familial MD cases, but only 1 heterozygous likely pathogenic variant in the OTOG gene (rs552304627) was found in 2 unrelated families. The gene burden analysis found an enrichment of rare missense variants in the OTOG gene in familial MD. So, 15 of 46 families (33%) showed at least 1 rare missense variant in the OTOG gene, suggesting a key role in familial MD.

CONCLUSIONS: The authors found an enrichment of multiplex rare missense variants in the OTOG gene in familial MD. This finding supports OTOG as a relevant gene in familial MD and set the groundwork for genetic testing in MD.

PMID: 32251013 [PubMed – as supplied by publisher]

PubMed:32251013

Solute carrier family 4 member 1 might participate in the pathogenesis of Meniere’s disease in a murine endolymphatic hydrop model

September 19, 2019

https://www.tandfonline.com/doi/abs/10.1080/00016489.2019.1663365?journalCode=ioto20

https://www.ncbi.nlm.nih.gov/pubmed/31536436?dopt=Abstract

Solute carrier family 4 member 1 might participate in the pathogenesis of Meniere’s disease in a murine endolymphatic hydrop model.

Acta Otolaryngol. 2019 Sep 19;:1-11

Authors: Sun S, Zhang D, Sun G, Song Y, Cai J, Fan Z, Wang H

Abstract

Background: To date, the pathogenesis of Meniere’s disease (MD) remains unclear. Previous research found that the SLC4A1 gene significantly down-regulated. Aims: This study sought to understand the effect of SLC4A1 on the pathogenesis of MD. ELH C57 mice models were induced by intraperitoneal injection of AVP. Material and methods: The mRNA expression levels of SLC4A1, SLC4A10 and SLC26A4 were monitored by real-time quantitative PCR, the protein expression levels of SLC4A1 were monitored by immunoblotting and immunofluorescence before and after the ELH. DIDS is an inhibitor of SLC4A1. The expression levels of SLC4A1 were also monitored in the AVP + DIDS group. Results: We successfully established the model of ELH after applied AVP. The results of HE staining showed displacement of Reissner’s membrane with bulge to scala vestibule in ears of the AVP group. Cochlea/ELS SLC4A1 protein and SLC4A1, SLC4A10, SLC26A4 mRNA expressions were reduced significantly in C57 mice of the AVP group. The SLC4A1 protein expression levels and SLC4A1, SLC4A10, SLC26A4 mRNA expression levels declined more obvious in the cochlea and ELS in C57 mice of the AVP + DIDS group. Conclusions and significance: SLC4A1 was a protective factor in the pathogenesis of MD, but the mechanisms were unknown.

PMID: 31536436 [PubMed – as supplied by publisher]

PubMed:31536436