Roberto Silva-Rojas, Laura Pérez-Guàrdia, Alix Simon, Sarah Djeddi, Susan Treves, Agnès Ribes, Lorenzo Silva-Hernández, Céline Tard, Jocelyn Laporte, Johann Böhm
Tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK) are clinically overlapping disorders characterized by childhood-onset muscle weakness and a variable occurrence of multisystemic signs, including short stature, thrombocytopenia, and hyposplenism. TAM/STRMK is caused by gain-of-function mutations in the Ca2+ sensor STIM1 or the Ca2+ channel ORAI1, both of which regulate Ca2+ homeostasis through the ubiquitous store-operated Ca2+ entry (SOCE) mechanism. Functional experiments in cells have demonstrated that the TAM/STRMK mutations induce SOCE overactivation, resulting in excessive influx of extracellular Ca2+...
March 5, 2024: JCI Insight