A Novel R140S γc Variant Alters Cellular Distribution, Reduces Surface Expression, and Impairs Cytokine Signaling in Atypical X-SCID.

ABSTRACT: The interleukin-2 receptor γ (IL-2Rγ, or γc) is a crucial component of several cytokine receptor complexes. Deficiencies in γc lead to X-linked severe combined immunodeficiency (X-SCID), characterized by recurrent infections due to the absence or dysfunction of T and NK cells, and nonfunctional B cells. Missense variants in the γc extracellular region are linked to atypical X-SCID with normal counts of T, B, and NK cells and less severe symptoms, yet the underlying cellular and molecular mechanisms are not well understood. This study describes a case of atypical X-SCID with a missense variant (c.420 A > T, p.R140S) in the γc extracellular domain, associated with recurrent bacterial, fungal, and viral infections. We found that the R140S variant leads to reduced surface expression and variab

SUBMITTER: Dong L 

PROVIDER: S-EPMC12317921 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature