Burden of novel and ultra-rare missense variants in the NF-κB pathway genes associated to Ménière's disease

Ménière's disease (MD) is an inner ear disorder characterised by tinnitus, sensorineural hearing loss and dizziness, although around 60% of patients also exhibit and immune dysregulation. Transcriptomic studies have identified three distinct immune phenotypes in MD, classified based on systemic inflammation, cytokine profiles and association to autoinflammatory/autoimmune comorbidities....

No actionable clinical change yet — these findings are exploratory genetic association data; further validation studies are needed before NF-κB pathway testing has a role in Ménière's disease diagnosis or management.

Identifying an immune-genetic basis for Ménière's disease could open new therapeutic targets and improve patient stratification, which is significant given the condition's poorly understood aetiology.

1. 01Novel and ultra-rare missense variants (rare gene spelling changes) in NF-κB pathway genes were studied in Ménière's disease patients.
2. 02The NF-κB pathway is a key regulator of immune and inflammatory responses.
3. 03Findings suggest an increased burden of rare variants in this pathway among affected individuals.
4. 04Published in Frontiers in Immunology (2026).
5. 05Results are preliminary; the study does not establish causation.

PMID

42220536

DOI

10.3389/fimmu.2026.1789753.

Journal

Frontiers in Immunology

Publication type

research_article

Evidence level

3

Population

Individuals with Ménière's disease presenting with tinnitus, sensorineural hearing loss, and dizziness

Intervention

Genetic burden analysis of novel and ultra-rare missense variants in NF-κB pathway genes

Comparator

Controls without Ménière's disease (implied)