Work

Germline gain-of-function mutation of STAT1 rescued by somatic mosaicism in immune dysregulation-polyendocrinopathy-enteropathy-X-linked-like disorder

Year: 2019

Type: article

Abstract: Gain-of-function (GoF) mutations of signal transducer and activator of transcription 1 (STAT1) cause broad immune dysfunction ranging from simple immunodeficiency to complex immune disorders.1 These mutations are frequently enriched in the coiled-coil domain or DNA-binding domain of STAT1 (Fig 1, A).2,3 STAT1 GoF mutations lead to the uncontrolled phosphorylation of STAT1, which disrupts STAT1-dependent clonal expansion and memory formation of CD8+ T cells.4,5 The most frequent clinical phenotype induced by STAT1 GoF mutations is simple immunodeficiency, for example, chronic mucocutaneous candidiasis (Fig 1, B).

Source: Journal of Allergy and Clinical Immunology

DOI: 10.1016/j.jaci.2019.11.028