Monoallelic expression can govern penetrance of inborn errors of immunity.

ABSTRACT: Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy¹. Incomplete penetrance is common among IEIs despite their monogenic basis². Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele^3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters allele expression commitment, in support of two proposed mechanisms^5,6 for the regulation of aRMAE. We tested

SUBMITTER: Stewart O 

PROVIDER: S-EPMC11804961 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature