Two rare mutations in homozygosity synergize to silence TREX1 in Aicardi-Goutieres syndrome.

ABSTRACT:

Background

Aicardi-Goutières syndrome (AGS) is a rare monogenic type I interferonopathy characterized by dysregulated inflammation and tissue damage that primarily affects the central nervous system. AGS is genetically diverse, with pathogenic variants across multiple genes, including TREX1, which drives excessive type I interferon (IFN) production.

Objective

This study investigated the genetic and molecular mechanisms underlying AGS in a family of two affected children, focusing on the role of TREX1 variants in protein expression and dysregulation of the interferon pathway.

Methods

Genomic sequencing data were used to identify TREX1 variants in the affected children. Functional assays in patient-derived lymphoblastoid cells (LCLs) and cell line models w

SUBMITTER: Rubin T 

PROVIDER: S-EPMC11885508 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature