Gain-of-function mutations in STIM1 and ORAI1 causing tubular aggregate myopathy and Stormorken syndrome

Cell Calcium
Johann Böhm, Jocelyn Laporte

Abstract

Calcium (Ca2+) is a key regulator for a large number of cellular functions in all kinds of cells, and small disturbances of Ca2+ homeostasis can severely compromise normal physiology in various tissues and organs. A major mechanism controlling Ca2+ homeostasis is store-operated Ca2+ entry (SOCE), which relies on the concerted action of the reticular Ca2+ sensor STIM1 and the plasma membrane Ca2+ channel ORAI1. Gain-of-function mutations in the respective genes induce excessive Ca2+ entry, and cause tubular aggregate myopathy (TAM) and Stormorken syndrome. Both disorders are part of a clinical continuum and involve muscle weakness and additional variably pronounced features including miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. Mutations in the reticular Ca2+ buffer calsequestrin (CASQ1) have moreover been associated with the mild end of the TAM/Stormorken syndrome spectrum. Here we review the clinical and histological characteristics of both disorders, provide an overview on the genetic causes, and thereby focus on the pathomechanisms leading to muscle dysfunction and the multi-systemic phenotype of tubular aggregate myopathy and Stormorken syndrome.

Citations

Feb 15, 2019·Journal of Child Neurology·Ang LiAndrew J Waclawik
Nov 2, 2019·Disease Models & Mechanisms·Celia Cordero-SanchezArmando A Genazzani
Feb 29, 2020·Journal of Cell Science·Liling NiuQian Wang
Feb 11, 2020·Brain : a Journal of Neurology·Joery P MolenaarDamien Sternberg
Aug 11, 2020·American Journal of Medical Genetics. Part a·Sandra DonkervoortCarsten G Bönnemann
Jun 4, 2020·Journal of Muscle Research and Cell Motility·Daniela RossiVincenzo Sorrentino
May 28, 2020·International Journal of Molecular Sciences·Megan NoblePeter B Stathopulos
Jun 27, 2020·The Journal of General Physiology·Joseph L DynesMichael D Cahalan
Jul 30, 2019·Journal of Neuromuscular Diseases·Vanessa SchartnerJohann Böhm
Aug 20, 2020·Journal of Muscle Research and Cell Motility·Feliciano ProtasiSimona Boncompagni
Oct 20, 2020·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Georges Arielle PecheJohann Böhm
Sep 24, 2020·Annual Review of Pharmacology and Toxicology·Daniel BakowskiAnant B Parekh
Jun 24, 2020·Cell Calcium·Qian Wang, Marek Michalak
Apr 17, 2021·Hämostaseologie·N A PodoplelovaM A Panteleev
Jul 15, 2021·Nature Reviews. Molecular Cell Biology·James J DowlingMelissa J Spencer
Aug 20, 2021·Frontiers in Neurology·Li-Jun JiangZan-Hua Rong
Aug 10, 2021·Muscle & Nerve·Chiara TicciLuciano Merlini

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