CASQ1 mutations impair calsequestrin polymerization and cause tubular aggregate myopathy
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Tubular aggregate myopathy (TAM) is a rare muscle disorder characterized by abnormal accumulations of membrane tubules in muscle fibers, and marked by progressive muscle weakness, cramps, and myalgia . Genetically, TAM has been assigned to mutations in STIM1  and ORAI1 , both encoding key regulators of Ca2+ homeostasis. Through exome sequencing of molecularly undiagnosed TAM cases, we now identified CASQ1 as the third TAM gene, and we support our findings by clinical, histological, genetic, and functional data.
We thank the members of the families for their interest in this study, Wolfram Kress, Michel Fardeau, and Daniel Hantaï for material transfer, and Catherine Koch, Anaïs Chanut, and Raphaël Schneider for their valuable technical assistance. This work was funded by INSERM, CNRS, University of Strasbourg, Agence Nationale de la Recherche (ANR-11-BSV1-026, ANR-10-LABX-0030-INRT, ANR-10-IDEX-0002, and FRISBI ANR-10-INBS-05), Fondation Maladies Rares, Association Française contre les Myopathies (AFM-17088), the Muscular Dystrophy Association (MDA-186985), and the Swiss National Science Foundation (323530_158118 to MB). The EuroBioBank and Telethon Network of Genetic Biobanks (GTB12001F to MM) are gratefully acknowledged for providing biological samples.
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