Burden of novel and ultra-rare missense variants in the NF-κB pathway genes associated to Ménière's disease - PubMed
4 hours ago
- #NF-κB Pathway
- #Genetic Variants
- #Ménière's Disease
- Ménière's disease (MD) is an inner ear disorder often linked to immune dysregulation, with about 60% of patients affected, and it exhibits three distinct immune phenotypes based on systemic inflammation, cytokine profiles, and autoimmune comorbidities.
- The study analyzed exome data of NF-κB pathway genes, identifying ultrarare heterozygous variants in TLR9, TNFRSF1B, and FAS in MD patients, which may contribute to immune phenotypes.
- Splicing predictions indicated that variants in TLR9 and TNFRSF1B could create cryptic donor/acceptor sites, while protein modelling showed destabilizing effects and altered atomic interactions, potentially reducing binding efficiency in dimer models.
- The findings suggest that rare variants in TLR9, TNFRSF1B, and FAS are associated with autoinflammation, linking MD's immune phenotypes to comorbid autoimmune/autoinflammatory disorders.