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Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease

Meniere's disease (MD) is a clinical spectrum of rare disorders characterized by vertigo attacks, associated with sensorineural hearing loss (SNHL) and tinnitus involving low to medium frequencies. Although it shows familial aggregation with incomplete phenotypic forms and variable expressivity...

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Autores principales: Gallego-Martinez, Alvaro, Requena, Teresa, Roman-Naranjo, Pablo, Lopez-Escamez, Jose A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385525/
https://www.ncbi.nlm.nih.gov/pubmed/30828346
http://dx.doi.org/10.3389/fgene.2019.00076
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author Gallego-Martinez, Alvaro
Requena, Teresa
Roman-Naranjo, Pablo
Lopez-Escamez, Jose A.
author_facet Gallego-Martinez, Alvaro
Requena, Teresa
Roman-Naranjo, Pablo
Lopez-Escamez, Jose A.
author_sort Gallego-Martinez, Alvaro
collection PubMed
description Meniere's disease (MD) is a clinical spectrum of rare disorders characterized by vertigo attacks, associated with sensorineural hearing loss (SNHL) and tinnitus involving low to medium frequencies. Although it shows familial aggregation with incomplete phenotypic forms and variable expressivity, most cases are considered sporadic. The aim of this study was to investigate the burden for rare variation in SNHL genes in patients with sporadic MD. We conducted a targeted-sequencing study including SNHL and familial MD genes in 890 MD patients to compare the frequency of rare variants in cases using three independent public datasets as controls. Patients with sporadic MD showed a significant enrichment of missense variants in SNHL genes that was not found in the controls. The list of genes includes GJB2, USH1G, SLC26A4, ESRRB, and CLDN14. A rare synonymous variant with unknown significance was found in the MARVELD2 gene in several unrelated patients with MD. There is a burden of rare variation in certain SNHL genes in sporadic MD. Furthermore, the interaction of common and rare variants in SNHL genes may have an additive effect on MD phenotype. This study will contribute to design a gene panel for the genetic diagnosis of MD.
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spelling pubmed-63855252019-03-01 Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease Gallego-Martinez, Alvaro Requena, Teresa Roman-Naranjo, Pablo Lopez-Escamez, Jose A. Front Genet Genetics Meniere's disease (MD) is a clinical spectrum of rare disorders characterized by vertigo attacks, associated with sensorineural hearing loss (SNHL) and tinnitus involving low to medium frequencies. Although it shows familial aggregation with incomplete phenotypic forms and variable expressivity, most cases are considered sporadic. The aim of this study was to investigate the burden for rare variation in SNHL genes in patients with sporadic MD. We conducted a targeted-sequencing study including SNHL and familial MD genes in 890 MD patients to compare the frequency of rare variants in cases using three independent public datasets as controls. Patients with sporadic MD showed a significant enrichment of missense variants in SNHL genes that was not found in the controls. The list of genes includes GJB2, USH1G, SLC26A4, ESRRB, and CLDN14. A rare synonymous variant with unknown significance was found in the MARVELD2 gene in several unrelated patients with MD. There is a burden of rare variation in certain SNHL genes in sporadic MD. Furthermore, the interaction of common and rare variants in SNHL genes may have an additive effect on MD phenotype. This study will contribute to design a gene panel for the genetic diagnosis of MD. Frontiers Media S.A. 2019-02-15 /pmc/articles/PMC6385525/ /pubmed/30828346 http://dx.doi.org/10.3389/fgene.2019.00076 Text en Copyright © 2019 Gallego-Martinez, Requena, Roman-Naranjo and Lopez-Escamez. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Gallego-Martinez, Alvaro
Requena, Teresa
Roman-Naranjo, Pablo
Lopez-Escamez, Jose A.
Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease
title Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease
title_full Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease
title_fullStr Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease
title_full_unstemmed Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease
title_short Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease
title_sort excess of rare missense variants in hearing loss genes in sporadic meniere disease
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385525/
https://www.ncbi.nlm.nih.gov/pubmed/30828346
http://dx.doi.org/10.3389/fgene.2019.00076
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