Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease
Metadatos
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Frontiers Media
Materia
Meniere’s disease Variant aggregation Spanish population SNHL Vertigo
Fecha
2019-02-15Referencia bibliográfica
Gallego-Martinez A, Requena T, Roman-Naranjo P and Lopez-Escamez JA (2019) Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease. Front. Genet. 10:76.
Patrocinador
This study was funded by FPS-PI0496-2014 and EF-0247- 2017 from Consejeria de Salud, Spain, 2016-MeniereSociety Grant, UK and Luxembourg National Research Fund (INTER/Mobility/17/11772209).Resumen
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 sporadicMD. 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.