{Reference Type}: Journal Article
{Title}: Store-operated calcium entry dysfunction in CRAC channelopathy: Insights from a novel STIM1 mutation.
{Author}: Alary B;Cintas P;Claude C;Dellis O;Thèze C;Van Goethem C;Cossée M;Krahn M;Delague V;Bartoli M;
{Journal}: Clin Immunol
{Volume}: 265
{Issue}: 0
{Year}: 2024 Aug 6
{Factor}: 10.19
{DOI}: 10.1016/j.clim.2024.110306
{Abstract}: 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.