Functional validation of a novel STAT3 'variant of unknown significance' identifies a new case of STAT3 GOF syndrome and reveals broad immune cell defects.

ABSTRACT:

Introduction

Signal transducer and activator of transcription 3 (STAT3) orchestrates crucial immune responses through its pleiotropic functions as a transcription factor. Patients with germline monoallelic dominant negative or hypermorphic STAT3 variants, who present with immunodeficiency and/or immune dysregulation, have revealed the importance of balanced STAT3 signaling in lymphocyte differentiation and function, and immune homeostasis. Here, we report a novel missense variant of unknown significance in the DNA-binding domain of STAT3 in a patient who experienced hypogammaglobulinemia, lymphadenopathy, hepatosplenomegaly, immune thrombocytopenia, eczema, and enteropathy over a 35-year period.

Methods

In vitro demonstration of prolonged STAT3 activation due to delayed deph

SUBMITTER: Mackie J 

PROVIDER: S-EPMC11791529 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature