Allelic variants of genes KCNQ2 and KCNQ3 and tinnitus extreme phenotype in patients with Meniere's disease

Zusammenfassung

Meniere's disease (MD) is defined as a chronic disorder of unknown etiology, characterized by progressive sensorineural hearing loss (SNHL), predominantly in low and middle frequencies, tinnitus, aural fullness and recurrent vertigo crisis, with a duration of at least 20 minutes. Classically, the symptoms have been attributed to the accumulation of endolymph in the labyrinth (endolymphatic hydrops), but the causes that alter the homeostasis of the endolymph are not known. MD is a clinically heterogeneous disorder, possibly resulting from the interaction of multiple factors, such as allelic variants, the immune response and environmental factors that are not well known. Recent studies have described several clinical subtypes within MD, demonstrating the heterogeneity of this clinical entity. The objective of this thesis is to identify individuals with MD and tinnitus extreme phenotype (TEP) to determine if there is an enrichment of allelic variants of the KCNQ2 and KCNQ3 genes in this subgroup of patients. Thus, the first objective is to characterize the tinnitus in patients with MD. The second objective seeks the identification and selection of patients with MD and TEP, for the Whole Exome Sequencing (WES) and analysis of the allelic variants of the KCNQ2 and KCNQ3 genes of this subgroup of patients. The findings in this thesis support that: 1) Tinnitus is a heterogeneous symptom in patients with MD, which also suggests several potential mechanisms for tinnitus. 2) Most patients with MD develop a persistent, constant tinnitus, but few of them report an annoying tinnitus with a significant impact on their quality of life, to be considered a tinnitus extreme phenotype. 3) The type of tinnitus and the hearing involvement in MD show a significant correlation with the disability perceived by patients estimated by the THI. 4) There is no burden of non-synonymous rare variants in KCNQ2 and KCNQ3 genes in patients with MD.