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Acta Neuropathologica

, Volume 135, Issue 1, pp 149–151 | Cite as

CASQ1 mutations impair calsequestrin polymerization and cause tubular aggregate myopathy

  • Johann BöhmEmail author
  • Xavière Lornage
  • Frederic Chevessier
  • Catherine Birck
  • Simona Zanotti
  • Paola Cudia
  • Monica Bulla
  • Florence Granger
  • Mai Thao Bui
  • Maxime Sartori
  • Christiane Schneider-Gold
  • Edoardo Malfatti
  • Norma B. Romero
  • Marina Mora
  • Jocelyn LaporteEmail author
Correspondence

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 [3]. Genetically, TAM has been assigned to mutations in STIM1 [2] and ORAI1 [7], 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.

Family 1 has an ancestral history of a muscle phenotype segregating as a dominant disease, and a partial clinical and histological description was reported earlier [ 8]. Patient 103901 from Family 2 is a singleton. Birth, early childhood, and motor milestones were normal for all affected members from both families. Disease onset was between early 20s and mid-40s with a slowly progressive muscle weakness mainly involving the proximal muscles in the lower limbs for Family...

Notes

Acknowledgements

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.

Supplementary material

401_2017_1775_MOESM1_ESM.pdf (459 kb)
Supplementary material 1 (PDF 459 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Johann Böhm
    • 1
    Email author
  • Xavière Lornage
    • 1
  • Frederic Chevessier
    • 2
  • Catherine Birck
    • 1
  • Simona Zanotti
    • 3
  • Paola Cudia
    • 4
  • Monica Bulla
    • 5
  • Florence Granger
    • 1
  • Mai Thao Bui
    • 6
  • Maxime Sartori
    • 1
  • Christiane Schneider-Gold
    • 7
  • Edoardo Malfatti
    • 6
  • Norma B. Romero
    • 6
  • Marina Mora
    • 3
  • Jocelyn Laporte
    • 1
    Email author
  1. 1.IGBMC, Inserm U 964, CNRS UMR 7104University of StrasbourgIllkirchFrance
  2. 2.CureVac AGTübingenGermany
  3. 3.IRCCS Istituto Neurologico C. BestaMilanItaly
  4. 4.IRCCS San Camillo HospitalVeniceItaly
  5. 5.University of GenevaGenevaSwitzerland
  6. 6.Institut de MyologieParisFrance
  7. 7.Ruhr-University BochumBochumGermany

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