Excess of Rare Missense Variants in Hearing Loss Genes in Sporadic Meniere Disease Gallego Martínez, Álvaro Requena, Teresa Román-Naranjo, Pablo López Escámez, José Antonio Meniere’s disease Variant aggregation Spanish population SNHL Vertigo 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. 2020-01-30T12:00:26Z 2020-01-30T12:00:26Z 2019-02-15 info:eu-repo/semantics/article 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. http://hdl.handle.net/10481/59286 10.3389/fgene.2019.00076 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España Frontiers Media