The T385M STAT1 gain-of-function mutation confers the most severe disease outcomes.

ABSTRACT:

Background

Gain-of-function (GOF) mutations in STAT1 cause a combined immunodeficiency characterized by chronic mucocutaneous candidiasis (CMC), recurrent infections, and autoimmunity. Mutations in the DNA-binding domain (DBD) have previously been associated with poor outcomes, but the contributions of specific variants to clinical phenotype remain unexplored.

Methods

We performed a systematic literature review to identify patients with confirmed STAT1 GOF mutations, integrating new cases with a previously reported international cohort. Clinical and genetic data were analyzed at both domain and mutation level to define genotype-phenotype correlations.

Results

A total of 533 unique patients from 36 countries were identified, harboring 135 distinct mutatio

SUBMITTER: Torrance R 

PROVIDER: S-EPMC12698592 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature