Ryanodine receptor type 1 gene mutations found in the Canadian malignant hyperthermia population

摘要: Malignant hyperthermia (MH) is an autosomal dominant pharmacogenetic disorder that manifested on exposure of susceptible individuals to halogenated anesthetics or succinylcholine. Since MH associated primarily with mutations in the ryanodine receptor type 1 (RYR1) gene, purpose this study was determine distribution and frequency causative RyR1 Canadian (MHS) population. In study, we screened a representative cohort 36 unrelated MHS for RYR1 by sequencing complete transcripts selected regions CACNA1S transcripts. We then analyzed correlation between caffeine-halothane contracture test (CHCT) results genotypes within families. Eighty-six percent patients had at least one mutation (31 out 36), five which were who double-variant carriers. Fifteen 27 identified novel. Eight novel mutations, involving highly conserved amino acid residues, predicted be causal. Two co-segregated phenotype two large independent families (a total 79 individuals). Fourteen (five 36) carried neither nor known mutations. The population are close those European populations. Novel described will contribute worldwide pool MH-associated ultimately increasing value genetic diagnostic testing.