β-Actin Deficiency in Baraitser-Winter Syndrome Type 1 Disrupts T-Cell Function and Immune Regulation: Implications for Targeted Therapy in Actinopathies.

ABSTRACT:

Purpose

Baraitser-Winter syndrome type 1 (BRWS1) is a rare disorder characterized by intellectual disability, short stature, facial dysmorphism, cortical malformations, macrothrombocytopenia, and recurrent infections. BRWS1 is caused by loss-of-function variants in ACTB, leading to β-actin deficiency. Given the essential role of the actin cytoskeleton in T-cell activation, the immunological consequences of ACTB mutations remain unexplored. Here, we characterize immune dysfunction associated with a novel ACTB variant in a patient with BRWS1.

Methods

Whole-exome sequencing identified a heterozygous ACTB p.Gln360ProfsTer4 variant in a patient with BRWS1 and combined immunodeficiency. Functional studies were performed in HEK293T cells transfected with wild-type and mutant ACTB c

SUBMITTER: Bar-On Z 

PROVIDER: S-EPMC12316732 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature