Discovering patterns in the pathologic significance of non-missense deleterious variants in RELA - PubMed
5 hours ago
- #autoinflammatory disease
- #haploinsufficiency
- #RELA variants
- Monoallelic RELA variants causing haploinsufficiency (HI) are linked to mucocutaneous ulcers and enteritis.
- Dominant-negative (DN) RELA variants often show autoinflammatory phenotypes with type I interferonopathy.
- Most autosomal dominant RelA deficiency cases involve non-missense deleterious variants with premature stop codons.
- Amino acid P290 was identified as the boundary between RELA-HI and RELA-DN variants.
- Corticosteroids were less effective in RELA-DN patients, increasing reliance on biologics like anti-TNF agents.
- Atypical variants (missense and in-frame) were confirmed pathogenic through experimental verification.
- Non-missense RELA variants' positions help predict functional changes, aiding diagnosis of RelA deficiency.
- Missense variants require functional testing as their effects cannot be predicted by position alone.