MUTATION SCREENING OF THE RYR1 GENE IN MALIGNANT HYPERTHERMIA - DETECTION OF A NOVEL TYR TO SER MUTATION IN A PEDIGREE WITH ASSOCIATED CENTRAL CORES

The ryanodine receptor gene (RYR1) has been shown to be mutated in a s mall number of malignant hyperthermia (MH) pedigrees. Missense mutatio ns in this gene have also been identified in two families with central core disease (CCD), a rare myopathy closely associated with MH. In an effort to identify other RYR1 mutations responsible for MH and CCD, w e used a SSCP approach to screen the RYR1 gene for mutations in a fami ly exhibiting susceptibility to MH (MHS) where some of the MHS individ uals display core regions in their muscle. Sequence analysis of a uniq ue aberrant SSCP has allowed us to identify a point mutation cosegrega ting with MHS in the described family. The mutation changes a conserve d tyrosine residue at position 522 to a serine residue. This mutation is positioned relatively close to five of the six MHS/CCD mutations kn own to date and provides further evidence that MHS/CCD mutations may c luster in the amino terminal region of the RYR1 protein. (C) 1994 Acad emic Press, Inc.