Stormorken Syndrome

12/01/2023 - "Our results rule out activation of the CalDAG-GEFI/Rap1/integrin pathway as a major cause of thrombocytopenia in Stim1Sax miceOur findings help to narrow down potential causes of thrombocytopenia in disorders such as Stormorken syndrome."
12/01/2023 - "Platelets are small blood cells which act to prevent blood loss, which circulate in a resting state but are rapidly activated upon exposure to ligands at the site of vascular injuryCalcium (Ca2+) is critical for platelet activation, especially for activation of integrins which support platelet–platelet interactionsIf platelet activation occurs in circulation, platelets can be prematurely cleared from blood and unable to function in hemostasisDisorders of Ca2+ dysregulation such as Stormorken syndrome are associated with reduced platelet counts (thrombocytopenia) and bleedingWhat did we discover? "
06/01/2015 - "Next-generation sequencing technology (NGST), mainly exome sequencing, has highlighted genes responsible for defects in platelet secretion (NBEAL2, gray platelet syndrome), procoagulant activity (STIM1, Stormorken syndrome), and activation pathways (RASGRP2, CalDAG-GEFI deficiency and integrin dysfunction; PRKACG, cyclic adenosine monophosphate-dependent protein kinase deficiency). "

12/01/2023 - "Platelets are small blood cells which act to prevent blood loss, which circulate in a resting state but are rapidly activated upon exposure to ligands at the site of vascular injuryCalcium (Ca2+) is critical for platelet activation, especially for activation of integrins which support platelet–platelet interactionsIf platelet activation occurs in circulation, platelets can be prematurely cleared from blood and unable to function in hemostasisDisorders of Ca2+ dysregulation such as Stormorken syndrome are associated with reduced platelet counts (thrombocytopenia) and bleedingWhat did we discover? "

01/01/2023 - "The most frequently occurring mutation in patients with Stormorken syndrome is R304W, which destabilizes and extends the STIM1 C terminus independently of ER Ca2+ store depletion, causing constitutive binding to Orai1 and CRAC channel activation. "
01/01/2020 - "Hyperactivating CRAC channels are known to cause several human diseases, including Stormorken syndrome. "
03/18/2014 - "These data expand our understanding of the phenotypic spectrum of dysregulated CRAC channel signaling, advance our knowledge of the molecular function of the CRAC channel, and suggest new therapies aiming at attenuating store-operated Ca(2+) entry in the treatment of patients with Stormorken syndrome and related pathologic conditions. "
01/01/2019 - "Conversely, gain-of-function (GOF) mutations in ORAI1 and STIM1 are associated with tubular aggregate myopathy (TAM) and Stormorken syndrome due to constitutive CRAC channel activation. "
03/18/2014 - "Heterologous expression of STIM1 p.R304W results in constitutive activation of the CRAC channel in vitro, and spontaneous bleeding accompanied by reduced numbers of thrombocytes in zebrafish embryos, recapitulating key aspects of Stormorken syndrome. "

12/01/2018 - "In contrast to patients with Stormorken syndrome, STIM1 was downregulated in fibroblasts from Stim1R304W/R304W mice, which maintained SOCE despite constitutive protein activity. "
01/01/2023 - "Stormorken syndrome is a multiorgan hereditary disease caused by dysfunction of the endoplasmic reticulum (ER) Ca2+ sensor protein STIM1, which forms the Ca2+ release-activated Ca2+ (CRAC) channel together with the plasma membrane channel Orai1. "

01/01/2021 - "Objective: To identify the gene mutation of Stormorken syndrome and review the published Stromal Interaction Molecule 1 (STIM1) mutation phenotype. "
01/01/2019 - "Stormorken syndrome is a rare genetic disorder (MIM 185070) first reported in 1983 with thrombocytopenia, muscle weakness, asplenia, and miosis caused by a mutation of the stromal interaction molecule 1 ( STIM1) gene.1 The muscle weakness is caused by a myopathy with tubular aggregate formation. "

06/01/2015 - "Next-generation sequencing technology (NGST), mainly exome sequencing, has highlighted genes responsible for defects in platelet secretion (NBEAL2, gray platelet syndrome), procoagulant activity (STIM1, Stormorken syndrome), and activation pathways (RASGRP2, CalDAG-GEFI deficiency and integrin dysfunction; PRKACG, cyclic adenosine monophosphate-dependent protein kinase deficiency). "

01/01/2017 - "Missense mutations in the luminal domain have been associated with tubular aggregate myopathy (TAM), while cytosolic mutations can cause Stormorken syndrome, a multisystemic disease associating TAM with asplenia, thrombocytopenia, miosis, ichthyosis, short stature and dyslexia. "

12/01/2018 - "Mutations in the reticular Ca2+ buffer calsequestrin (CASQ1) have moreover been associated with the mild end of the TAM/Stormorken syndrome spectrum. "

01/01/2022 - "Gain-of-function mutations on STIM1 and ORAI1 genes are responsible for an increased store-operated calcium entry, and underlie the characteristic symptoms of three overlapping ultra-rare genetic disorders (i.e tubular aggregate myopathy, Stormorken syndrome, York platelet syndrome) that can be grouped as tubular aggregate myopathies. "

12/01/2018 - "Mutations in the reticular Ca2+ buffer calsequestrin (CASQ1) have moreover been associated with the mild end of the TAM/Stormorken syndrome spectrum. "

03/05/2024 - "ORAI1 inhibition as an efficient preclinical therapy for tubular aggregate myopathy and Stormorken syndrome."
03/18/2014 - "These data expand our understanding of the phenotypic spectrum of dysregulated CRAC channel signaling, advance our knowledge of the molecular function of the CRAC channel, and suggest new therapies aiming at attenuating store-operated Ca(2+) entry in the treatment of patients with Stormorken syndrome and related pathologic conditions. "