Case report and review of the literature: immune dysregulation in a large familial cohort due to a novel pathogenic RELA variant.

ABSTRACT:

Objective

To explore and define the molecular cause(s) of a multi-generational kindred affected by Bechet's-like mucocutaneous ulcerations and immune dysregulation.

Methods

Whole genome sequencing and confirmatory Sanger sequencing were performed. Components of the NFκB pathway were quantified by immunoblotting, and function was assessed by cytokine production (IL-6, TNF-α, IL-1β) after lipopolysaccharide (LPS) stimulation. Detailed immunophenotyping of T-cell and B-cell subsets was performed in four patients from this cohort.

Results

A novel variant in the RELA gene, p. Tyr349LeufsTer13, was identified. This variant results in premature truncation of the protein before the serine (S) 536 residue, a key phosphorylation site, resulting in enhanced degradation of the p6

SUBMITTER: Lecerf K 

PROVIDER: S-EPMC9960492 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature