Detection ofthe T1640C RYR1 mutation indicating malignant hyperthermia indogs.

Abstract

Malignant hyperthermia (MH) isaclinical syndrome exhibiting elevation ofexpired carbon dioxide, hyperthermia, muscle rigidity, rhabdomyolysis, acidosis and hyperkalaemia, aswell ascardiac dysrhythmia and renal failure. The syndrome manifests itself asaresponse toanaesthetic agents, such ase.g., halothane, desflurane, and succinylcholine. Depending onthe animal species, MHischaracterised byautosomal dominant orrecessive inheritance, and sofar two genes have been identified whose mutations can belinked toMH: RYR1 and CACNA1S. Indifferent species, various mutations ofthe RYR1 gene have been described which may underlie MH. One ofthese mutations indogs isT1640C, which results inthe substitution ofalanine for valine ofthe amino acid 547 (V547A)inthe RYR1 protein. Inour work, weaimed toinvestigate MHatthe DNA level byidentifying theT1640C mutation inagroup of50dogs. For this purpose weused the PCR-RFLP technique, and insix dogs also direct sequencing ofPCR products and subsequent comparison oftheir sequences with the RYR1 gene sequence inanonline database. The results ofour study show that none ofthe dogs analysed had any mutant allele oftheRYR1 gene, indicating that none should beaffected byMH.