A mutation in the human ryanodine receptor gene associated with central core disease

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Central core disease (CCD) is a morphologically distinct, autosomal dominant myopathy with variable clinical features. A close association with malignant hypertheria (MH) has been identified. Since MH and CCD genes have been linked to the skeletal muscle ryanodine receptor (RYR1) gene, cDNA sequence analysis was used to search for a causal RYR1 mutation in a CCD individual. The only amino acid substitution found was an Arg2434His mutation, resulting from the substitution of A for G7301. This mutation was linked to CCD with a lod score of 4.8 at a recombinant fraction of 0.0 in 16 informative meioses in a 130 member family, suggesting a causal relationship to CCD.

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Zhang, Y., Chen, H., Khanna, V. et al. A mutation in the human ryanodine receptor gene associated with central core disease. Nat Genet 5, 46–50 (1993) doi:10.1038/ng0993-46

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