Novel ORAI1 Mutation Disrupts Channel Trafficking Resulting in Combined Immunodeficiency.

ABSTRACT: Store-operated Ca²⁺ entry (SOCE) represents a predominant Ca²⁺ influx pathway in non-excitable cells. SOCE is required for immune cell activation and is mediated by the plasma membrane (PM) channel ORAI1 and the endoplasmic reticulum (ER) Ca²⁺ sensor STIM1. Mutations in the Orai1 or STIM1 genes abolish SOCE leading to combined immunodeficiency (CID), muscular hypotonia, and anhidrotic ectodermal dysplasia. Here, we identify a novel autosomal recessive mutation in ORAI1 in a child with CID. The patient is homozygous for p.C126R mutation in the second transmembrane domain (TM2) of ORAI1, a region with no previous loss-of-function mutations. SOCE is suppressed in the patient's lymphocytes, which is associated with impaired T cell proliferation and cytokine pro

SUBMITTER: Yu F 

PROVIDER: S-EPMC8249264 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature