Different Contribution of Missense and Loss-of-Function Variants to the Genetic Structure of Familial and Sporadic Meniere Disease.

ABSTRACT: Meniere disease (MD) is a chronic inner ear disorder with significant heritability. This study compares the burden of rare high- and moderate-impact coding variants in an MD cohort to determine whether genetic burden in sporadic MD (SMD) overlaps familial MD (FMD), potentially revealing hidden inheritance in SMD. Exome sequencing identified rare variants in unrelated FMD (N = 93) and SMD (N = 287) patients. Gene Burden Analysis (GBA) was performed, and candidate genes were prioritized using the number of variant carriers, inner-ear expression, and hearing/balance-related phenotypic annotations. FMD patients showed higher accumulation of missense and loss-of-function variants than SMD, especially in genes linked to auditory and vestibular function. GBA identified 269 enriched

SUBMITTER: Parra-Perez AM 

PROVIDER: S-EPMC12450834 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature