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Short title: RYR1 gene analysis in Malignant Hyperthermia
Full title: Detection of ryanodine receptor gene (RYR1) mutations in the South African Malignant Hyperthermia (MH) population
Malignant hyperthermia (MH) is a pharmocogenetic disorder of skeletal muscle that is triggered by volatile inhalation anaesthetics or depolarizing muscle relaxants. Genetic analysis has implicated mutations in the ryanodine receptor gene of the skeletal muscle (RYR1) which encodes the calcium release channel in the sarcoplasmic reticulum (SR) to be responsible for MH (Gillard et al., 1991; Zhang et al., 1993).The majority of RYR1 mutations discovered for MH are clustered in three regions; ranging from exons 2 to 17 (MH region one) and exons 39 to 46 (MH region two). These two regions encode the N terminus of the protein that forms the myoplasmic foot (Jurkat-Rott et al., 2000). Recently a third hotspot has been observed in the C-terminal region of the RYR1 within exons 95 to 102 (Lynch et al., 1999), this region encodes the luminal/transmembrane domain of the protein. The aim of this molecular investigation is to identify mutations within the C-terminal region within exons 100 and 101 of the RYR1 gene that have not yet previously been screened for, in thirty South African MH patients. This study will contribute to the broad aim of the MH research programme which is to screen all causative mutations of the RYR1 gene to determine if any of the mutations are responsible for the pathogenesis of MH in the South African population.
Short title: Mutations in mtDNA.
Full title: Mutation screening of three mtDNA regions in South African paediatric patients with suspected mitochondrial disorders.
Mitochondria are important organelles in the body in that they produce energy in the form of ATP and heat from fuel molecules (carbohydrates, proteins and lipids). Mitochondria and the nucleus are the only cell organelles that contain their own DNA, but the mtDNA mutation rate is about 20 times higher than that of nDNA. MELAS, MERRF and LS are three of the most common mitochondrial disorders with mutations in certain mitochondrial genes. In this investigation, blood samples will be obtained from South African paediatric patients who were clinically diagnosed with suspected mitochondrial disorders and screened for mutations in the tRNA Leu(UUR) , tRNA Lys and ATPase 6 genes. The knowledge from this investigation can be used for the development of a future diagnostic service, and currently for informed genetic counselling of affected individuals and their family members.
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