%0 Journal Article
%T Store-operated calcium entry dysfunction in CRAC channelopathy: Insights from a novel STIM1 mutation.
%A Alary B
%A Cintas P
%A Claude C
%A Dellis O
%A Thèze C
%A Van Goethem C
%A Cossée M
%A Krahn M
%A Delague V
%A Bartoli M
%J Clin Immunol
%V 265
%N 0
%D 2024 Aug 6
%M 38977117
%F 10.19
%R 10.1016/j.clim.2024.110306
%X Store-operated calcium entry (SOCE) plays a crucial role in maintaining cellular calcium homeostasis. This mechanism involves proteins, such as stromal interaction molecule 1 (STIM1) and ORAI1. Mutations in the genes encoding these proteins, especially STIM1, can lead to various diseases, including CRAC channelopathies associated with severe combined immunodeficiency. Herein, we describe a novel homozygous mutation, NM_003156 c.792-3C > G, in STIM1 in a patient with a clinical profile of CRAC channelopathy, including immune system deficiencies and muscle weakness. Functional analyses revealed three distinct spliced forms in the patient cells: wild-type, exon 7 skipping, and intronic retention. Calcium influx analysis revealed impaired SOCE in the patient cells, indicating a loss of STIM1 function. We developed an antisense oligonucleotide treatment that improves STIM1 splicing and highlighted its potential as a therapeutic approach. Our findings provide insights into the complex effects of STIM1 mutations and shed light on the multifaceted clinical presentation of the patient.