Journal Articles

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Subject: search.filters.subject.malignant hyperthermia

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    Conserving wildlife in a changing world: Understanding capture myopathy - A malignant outcome of stress during capture and translocation
    (Oxford University Press on behalf of The Society for Experimental Biology, 2019-07-05) Breed D; Meyer LCR; Steyl JCA; Goddard A; Burroughs R; Kohn TA; Fuller A
    The number of species that merit conservation interventions is increasing daily with ongoing habitat destruction, increased fragmentation and loss of population connectivity. Desertification and climate change reduce suitable conservation areas. Physiological stress is an inevitable part of the capture and translocation process of wild animals. Globally, capture myopathy - a malignant outcome of stress during capture operations - accounts for the highest number of deaths associated with wildlife translocation. These deaths may not only have considerable impacts on conservation efforts but also have direct and indirect financial implications. Such deaths usually are indicative of how well animal welfare was considered and addressed during a translocation exercise. Importantly, devastating consequences on the continued existence of threatened and endangered species succumbing to this known risk during capture and movement may result. Since first recorded in 1964 in Kenya, many cases of capture myopathy have been described, but the exact causes, pathophysiological mechanisms and treatment for this condition remain to be adequately studied and fully elucidated. Capture myopathy is a condition with marked morbidity and mortality that occur predominantly in wild animals around the globe. It arises from inflicted stress and physical exertion that would typically occur with prolonged or short intense pursuit, capture, restraint or transportation of wild animals. The condition carries a grave prognosis, and despite intensive extended and largely non-specific supportive treatment, the success rate is poor. Although not as common as in wildlife, domestic animals and humans are also affected by conditions with similar pathophysiology. This review aims to highlight the current state of knowledge related to the clinical and pathophysiological presentation, potential treatments, preventative measures and, importantly, the hypothetical causes and proposed pathomechanisms by comparing conditions found in domestic animals and humans. Future comparative strategies and research directions are proposed to help better understand the pathophysiology of capture myopathy.
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    Pathogenicity assessment of seven RYR1 variants in patients with confirmed susceptibility to malignant hyperthermia in the Netherlands.
    (Elsevier Ltd on behalf of British Journal of Anaesthesia, 2025-01-30) van den Bersselaar LR; Schiemann AH; Yang C-Y; Voermans NC; Malagon I; Scheffer G-J; Bjorksten AR; Gillies R; Hellblom A; Kamsteeg E-J; Snoeck MMJ; Stowell KM; Hemmings HC
    Background Malignant hyperthermia (MH) susceptibility is associated with variants in RYR1, the gene encoding the skeletal muscle ryanodine receptor-1 (RyR1), in 70–75% of patients. Functional characterisation demonstrating an increased sensitivity to RyR1 agonists is necessary among other criteria for inclusion in the European Malignant Hyperthermia Group list of MH susceptibility diagnostic variants. Methods Seven variants in the RYR1 gene, p.Glu342Lys, p.Leu2288Ser, p.Phe2340Leu, p.Arg2676Trp, p.Val3324Ala, p.Phe4076Leu, and p.Trp5020Cys, identified in MH-susceptible individuals were introduced into the cDNA for the human RYR1 gene. These variants were tested in cultured human embryonic kidney HEK293 cells for their effect on calcium release in response to the RyR1 agonist 4-chloro-m-cresol. Calcium release of each variant was compared with wild-type and benign and pathogenic controls. Each variant was subjected to curation using the European Malignant Hyperthermia Group scoring matrix and ClinGen RYR1 Variant Curation Expert Panel guidelines. Results Six of seven RYR1 variants (p.Glu342Lys, p.Leu2288Ser, p.Phe2340Leu, p.Arg2676Trp, p.Val3324Ala, p.Phe4076Leu) showed hypersensitivity to 4-chloro-m-cresol compared with wild-type. The p.Trp5020Cys variant did not release calcium in response to 4-chloro-m-cresol. All variants had minor allele frequencies <0.1%. Rare exome variant ensemble learner scores of p.Glu342Lys, p.Leu2288Ser, p.Phe4076Leu, and p.Trp5020Cys were >0.85, supporting pathogenicity. Conclusions The variants p.Glu342Lys, p.Leu2288Ser p.Phe2340Leu, and p.Arg2676Trp are pathogenic or likely pathogenic for MH and can be used for presymptomatic testing for MH susceptibility. As current knowledge on the p.Val3324Ala, p.Phe4076Leu, and p.Trp5020Cys variants remains insufficient, they are still classified as variants of uncertain significance.