Résumé :
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Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic disease triggered by commonly used volatile anaesthetics and/or succinylcholine. In vitro muscle contracture testing (IVCT) is the gold standard test to establish an individual's risk of MH susceptibility (MHS) (2) while investigations of muscle energetics (1) and genetic analyses are commonly performed in order to better understand the genetic and metabolic bases of this infraclinical myopathy. MHS is characterised by a genetic heterogeneity and two genes, RYR1 and CACNA1S, have been associated with the disease. 29 causative mutations have been reported so far in the RYR1 gene. We report in the present study the results of 80 MHS families investigated in Marseilles. Among these 80 families, 44 have been genetically investigated. One causative mutation has been found in 17 families i.e. the porcine mutation (G341R) in 6 families and the R2458H mutation in two other families. A double mutation (R2676W/T2787S) has been reported in a single family (3)and so far the causative aspect of each of them is discussed. In four families, a single mutation has been found but the causative feature has not been clearly established. Among them, the T2787S mutation is present. Finally, none of the 20 common mutations has been found in the 22 remaining families. For these families, further investigations should have to be performed on mRNA from muscle samples. Overall, mutations in the RYR1 gene have been found in half of the investigated families. For the 50% remaining, additional investigations should be performed either in the RYR1 gene or in other candidate genes such as the gene coding for the DHPR receptor. 1. Bendahan D, Kozak-Ribbens G, Rodet L, Confort-Gouny S, and Cozzone PJ. 31Phosphorus magnetic resonance spectroscopy characterization of muscular metabolic anomalies in patients with malignant hyperthermia: application to diagnosis. Anesthesiology 88: 96-107, 1998. 2. Bendahan D, Guis S, Monnier N, Kozak-Ribbens G, Lunardi J, Ghattas B, Mattei JP, and Cozzone PJ. Comparative analysis of in vitro contracture tests with ryanodine and a combination of ryanodine with either halothane or caffeine: a comparative investigation in malignant hyperthermia. Acta Anaesthesiol Scand 48: 1019-1027, 2004. 3. Guis S, Figarella-Branger D, Monnier N, Bendahan D, Kozak-Ribbens G, Mattei JP, Lunardi J, Cozzone PJ, and Pellissier JF. Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization. Arch Neurol 61: 106-113, 2004.
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