Malignant hyperthermia (MH) is a clinical syndrome exhibiting elevation of expired carbon dioxide, hyperthermia, muscle rigidity, rhabdomyolysis, acidosis and hyperkalaemia, as well as cardiac dysrhythmia and renal failure. The syndrome manifests itself as a response to anaesthetic agents, such as e.g., halothane, desflurane, and succinylcholine. Depending on the animal species, MH is characterised by autosomal dominant or recessive inheritance, and so far two genes have been identified whose mutations can be linked to MH: RYR1 and CACNA1S. In different species, various mutations of the RYR1 gene have been described which may underlie MH. One of these mutations in dogs is T1640C, which results in the substitution of alanine for valine of the amino acid 547 (V547A) in the RYR1 protein. In our work, we aimed to investigate MH at the DNA level by identifying the T1640C mutation in a group of 50 dogs. For this purpose we used the PCR-RFLP technique, and in six dogs also direct sequencing of PCR products and subsequent comparison of their sequences with the RYR1 gene sequence in an online database. The results of our study show that none of the dogs analysed had any mutant allele of the RYR1 gene, indicating that none should be affected by MH.

Department of Biology and Physiology University of Veterinary Medicine and Pharmacy in Košice Košice Slovak Republic

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Brunson DB, Hogan K, Powers PA, Gregg R, Nelson TE. Investigation of the causal mutation for malignant hyperthermia in black Labrador Retrievers [abstract]. Canine Pract. 1998;23:48a.

Brunson DB, Hogan KJ. Malignant hyperthermia: A syndrome not a disease. Vet Clin North Am Small Anim Pract. 2004 Nov;34(6):1419-33. PubMed

Guzel O, Yildar E, Karan B, Aydin D, Mckinstry DC. Unusual hyperthermia related to general anaesthesia in an Anatolian shepherd dog. Vet Med-Czech. 2018 Nov;63(1):36-9.

Halliday NJ. Malignant hyperthermia. J Craniofac Surg. 2003 Sep;14(5):800-2. PubMed

Jiang D, Chen W, Xiao J, Wang R, Kong H, Jones PP, Zhang L, Fruen B, Chen SR. Reduced threshold for luminal Ca2+ activation of RyR1 underlies a causal mechanism of porcine malignant hyperthermia. J Biol Chem. 2008 Jul 25;283(30):20813-20. PubMed PMC

Larach MG, Landis JR, Bunn JS, Diaz M. Prediction of malignant hyperthermia susceptibility in low-risk subjects. An epidemiologic investigation of caffeine halothane contracture responses. The North American Malignant Hyperthermia Registry. Anesthesiology. 1992 Jan;76(1):16-27. PubMed

Lawal TA, Wires ES, Terry NL, Dowling JJ, Todd JJ. Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: A comprehensive scoping review of works published 1990–2019. Orphanet J Rare Dis. 2020 May 7;15(1):113. PubMed PMC

Mealey KL, Martinez SE, Villarino NF, Court MH. Personalized medicine: Going to the dogs? Hum Genet. 2019 May;138(5):467-81. PubMed

O’Brien PJ, Cribb PH, White RJ, Olfert ED, Steiss JE. Canine malignant hyperthermia: Diagnosis of susceptibility in a breeding colony. Can Vet J. 1983 Jun;24(6):172-7. PubMed PMC

Otto K. Maligne Hyperthermie als Narkosekomplikation beim Hund [Malignant hyperthermia as a complication of anesthesia in the dog]. Tierarztl Prax. 1992 Oct;20(5):519-22. German. PubMed

Roberts MC, Mickelson JR, Patterson EE, Nelson TE, Armstrong PJ, Brunson DB, Hogan K. Autosomal dominant canine malignant hyperthermia is caused by a mutation in the gene encoding the skeletal muscle calcium release channel (RYR1). Anesthesiology. 2001 Sep;95(3):716-25. PubMed

Rosenberg H, Pollock N, Schiemann A, Bulger T, Stowell K. Malignant hyperthermia: A review. Orphanet J Rare Dis. 2015 Aug 4;10:93. PubMed PMC

Sambuughin N, Holley H, Muldoon S, Brandom BW, de Bantel AM, Tobin JR, Nelson TE, Goldfarb LG. Screening of the entire ryanodine receptor type 1 coding region for sequence variants associated with malignant hyperthermia susceptibility in the north american population. Anesthesiology. 2005 Mar;102(3):515-21. PubMed

Satsangi J, Jewell DP, Welsh K, Bunce M, Bell JI. Effect of heparin on polymerase chain reaction. Lancet. 1994 Jun 11;343(8911):1509-10. PubMed

Short CE, Paddleford RR. Letter: Malignant hyperthermia in the dog. Anesthesiology. 1973 Oct;39(4):462-3. PubMed

The European Malignant Hyperpyrexia Group. A protocol for the investigation of malignant hyperpyrexia (MH) susceptibility. Brit J Anaesth. 1984 Nov;56(11):1267-9. PubMed

Thrift E, Wimpole JA, Child G, Brown N, Gandolfi B, Malik R. Exercise-induced hyperthermia syndrome (canine stress syndrome) in four related male English Springer Spaniels. Vet Med (Auckl). 2017 Sep 1;8:59-68. PubMed PMC

Yokota M, Tatsumi N, Nathalang O, Yamada T, Tsuda I. Effects of heparin on polymerase chain reaction for blood white cells. J Clin Lab Anal. 1999;13(3):133-40. PubMed PMC