Mutations in RYR1 in malignant hyperthermia and central core disease

Authors

  • Rachel Robinson,

    Corresponding author
    1. Malignant Hyperthermia (MH) Investigation Unit, Academic Unit Anaesthesia, St James' University Hospital, Leeds, United Kingdom
    • MH Investigation Unit, Academic Unit Anaesthesia, St James' University Hospital, Leeds LS9 7TF, United Kingdom
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  • Danielle Carpenter,

    1. Malignant Hyperthermia (MH) Investigation Unit, Academic Unit Anaesthesia, St James' University Hospital, Leeds, United Kingdom
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  • Marie-Anne Shaw,

    1. Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
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  • Jane Halsall,

    1. Malignant Hyperthermia (MH) Investigation Unit, Academic Unit Anaesthesia, St James' University Hospital, Leeds, United Kingdom
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  • Philip Hopkins

    1. Malignant Hyperthermia (MH) Investigation Unit, Academic Unit Anaesthesia, St James' University Hospital, Leeds, United Kingdom
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  • Communicated by Jacques S. Beckmann

Abstract

The RYR1 gene encodes the skeletal muscle isoform ryanodine receptor and is fundamental to the process of excitation–contraction coupling and skeletal muscle calcium homeostasis. Mapping to chromosome 19q13.2, the gene comprises 106 exons and encodes a protein of 5,038 amino acids. Mutations in the gene have been found in association with several diseases: the pharmacogenetic disorder, malignant hyperthermia (MH); and three congenital myopathies, including central core disease (CCD), multiminicore disease (MmD), and in an isolated case of a congenital myopathy characterized on histology by cores and rods. The majority of gene mutations reported are missense changes identified in cases of MH and CCD. In vitro analysis has confirmed that alteration of normal calcium homeostasis is a functional consequence of some of these changes. Genotype–phenotype correlation studies performed using data from MH and CCD patients have also suggested that mutations may be associated with a range of disease severity phenotypes. This review aims to summarize the current understanding of RYR1 mutations reported in association with MH and CCD and the present viewpoint on the use of mutation data to aid clinical diagnosis of these conditions. Hum Mutat 27(10), 977–989, 2006. © 2006 Wiley-Liss, Inc.

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