A MUTATION IN THE HUMAN RYANODINE RECEPTOR GENE ASSOCIATED WITH CENTRAL CORE DISEASE

Central core disease (CCD) is a morphologically distinct, autosomal do minant myopathy with variable clinical features. A close association w ith malignant hypertheria (MH) has been identified. Since MH and CCD g enes have been linked to the skeletal muscle ryanodine receptor (RYR1) gene, cDNA sequence analysis was used to search for a causal RYR1 mut ation 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 recombi nant fraction of 0.0 in 16 informative meioses in a 130 member family, suggesting a causal relationship to CCD.