RT Journal Article
T1 Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease.
A1 Gallego-Martinez, Alvaro
A1 Requena, Teresa
A1 Roman-Naranjo, Pablo
A1 Lopez-Escamez, Jose A
K1 Meniere's disease
K1 SNHL
K1 Spanish population
K1 variant aggregation
K1 vertigo
AB 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.
SN 1664-8021
YR 2019
FD 2019-02-15
LK https://hdl.handle.net/10668/26480
UL https://hdl.handle.net/10668/26480
LA en
DS RISalud
RD Apr 5, 2025