Sequencing of genes involved in the movement of calcium across human skeletal muscle sarcoplasmic reticulum: continuing the search for genes associated with malignant hyperthermia
| Autor: | D. Du Sart, Andrew R. Bjorksten, R. L. Gillies, B. M. Hockey |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Calcium Channels L-Type Critical Care and Intensive Care Medicine Calsequestrin medicine.disease_cause Sarcoplasmic Reticulum Calcium-Transporting ATPases 03 medical and health sciences 0302 clinical medicine 030202 anesthesiology Medicine Humans Muscle Skeletal Gene RYR1 Genetics Mutation business.industry Ryanodine receptor Malignant hyperthermia Skeletal muscle Biological Transport Anatomy medicine.disease Minor allele frequency Sarcoplasmic Reticulum 030104 developmental biology Anesthesiology and Pain Medicine medicine.anatomical_structure Calcium Calcium Channels business Malignant Hyperthermia |
| Zdroj: | Anaesthesia and intensive care. 44(6) |
| ISSN: | 0310-057X |
| Popis: | The genetic basis of malignant hyperthermia (MH) is not fully characterised and likely involves more than just the currently classified mutations in the gene encoding the skeletal muscle ryanodine receptor ( RYR1) and the gene encoding the α1 subunit of the dihydropyridine receptor ( CACNA1S). In this paper we sequence other genes involved in calcium trafficking within skeletal muscle in patients with positive in vitro contracture tests, searching for alternative genes associated with MH. We identified four rare variants in four different genes ( CACNB1, CASQ1, SERCA1 and CASQ2) encoding proteins involved in calcium handling in skeletal muscle in a cohort of 30 Australian MH susceptible probands in whom prior complete sequencing of RYR1 and CACNA1S had yielded no rare variants. These four variants have very low minor allele frequencies and while it is tempting to speculate that they have a role in MH, they remain at present variants of unknown significance. Nevertheless they provide the basis for a new set of functional studies, which may indeed identify novel players in MH. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|