Mutations in the gene–encoding SERCA1, the fast–twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease (original) (raw)

Nature Genetics volume 14, pages 191–194 (1996)Cite this article

Abstract

Brody disease is a rare inherited disorder of skeletal muscle function. Symptoms include exercise-induced impairment of skeletal muscle relaxation, stiffness and cramps. Ca2+ uptake and Ca2+ ATPase activities are reduced in the sarcoplasmic reticulum1–7, leading to the prediction that Brody disease results from defects in the ATP2A1 gene on chromosome 16p12.1–12.2, encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase. A recent search, however, did not reveal any mutations in the ATP2A1 gene in three Brody patients8. We have now associated Brody disease with the autosomal recessive inheritance of three ATP2A1 mutations in two families, suggesting that the disease is genetically heterogeneous. One mutation occurs at the splice donor site of intron 3, while the other two mutations lead to premature stop codons, truncating SERCA1, deleting essential functional domains and raising the intriguing question: how have these Brody patients partially compensated for the functional knockout of a gene product believed to be essential for fast-twitch skeletal muscle relaxation?

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Authors and Affiliations

  1. Banting and Best Department of Medical Research, University of Toronto, Charles H. Best Institute, 112 College St., Toronto, Ontario, M5G 1L6, Canada
    Alex Odermatt, Vijay K. Khanna & David H. MacLennan
  2. Department of Human Genetics, Sylvius Laboratories, Leiden University, P.O. Box 9503, Wassenaarseweg 72, 2300 RA, Leiden, The Netherlands
    Peter E. M. Taschner & Martijn H. Breuning
  3. Department of Neurology, Erasmus University, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands
    Herman F. M. Busch
  4. Montreal Neurological Institute, McGill University, 3801 Rue University, Montreal, Quebec, H3A2B4, Canada
    George Karpati
  5. Departmentof Neuroscience, University of California at San Diego, 550 Washington Street, Suite 221, San Diego, California, 92103, USA
    Charles K. Jablecki
  6. Department of Clinical Genetics, Erasmus University, Dr. Molewaterplein 50, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands
    Martijn H. Breuning

Authors

  1. Alex Odermatt
  2. Peter E. M. Taschner
  3. Vijay K. Khanna
  4. Herman F. M. Busch
  5. George Karpati
  6. Charles K. Jablecki
  7. Martijn H. Breuning
  8. David H. MacLennan

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Correspondence toDavid H. MacLennan.

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Odermatt, A., Taschner, P., Khanna, V. et al. Mutations in the gene–encoding SERCA1, the fast–twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease.Nat Genet 14, 191–194 (1996). https://doi.org/10.1038/ng1096-191

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