Adult muscle sodium channel α-subunit is a gene candidate for malignant hyperthermia susceptibility

Olckers, Antonel; Meyers, Deborah A.; Meyers, Samuel P.; Taylor, Eugene W.; Fletcher, Jeffrey E.; Rosenberg, Henry; Isaacs, H; Levitt, Roy C.

doi:10.1016/s0888-7543(05)80206-x

Cited by 42 publications

(12 citation statements)

References 15 publications

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“…In North America, the first alternative locus to chromosome 19q was assigned to chromosome 17q11.2-q24, 90 the MHS-2 locus, suggesting the voltage-dependent sodium channel of skeletal muscle membrane as a candidate gene. 112,123,168 The findings could not be confirmed in Europe 69,156 perhaps pointing to a regional type of MH or to the fact that myotonic syndromes caused by sodium channel mutations predispose to MH-like events. 141 Suggestions of further loci have been made not only for MH, 142 but also for CCD.…”

Section: Secondary Locimentioning

confidence: 89%

Genetics and pathogenesis of malignant hyperthermia

2000

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Malignant hyperthermia (MH) is a potentially life-threatening event in response to anesthetic triggering agents, with symptoms of sustained uncontrolled skeletal muscle calcium homeostasis resulting in organ and systemic failure. Susceptibility to MH, an autosomal dominant trait, may be associated with congenital myopathies, but in the majority of the cases, no clinical signs of disease are visible outside of anesthesia. For diagnosis, a functional test on skeletal muscle biopsy, the in vitro contracture test (IVCT), is performed. Over 50% of the families show linkage of the IVCT phenotype to the gene encoding the skeletal muscle ryanodine receptor and over 20 mutations therein have been described. At least five other loci have been defined implicating greater genetic heterogeneity than previously assumed, but so far only one further gene encoding the main subunit of the voltage-gated dihydropyridine receptor has a confirmed role in MH. As a result of extensive research on the mechanisms of excitation-contraction coupling and recent functional characterization of several disease-causing mutations in heterologous expression systems, much is known today about the molecular etiology of MH.

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Section: Secondary Locimentioning

confidence: 89%

Genetics and pathogenesis of malignant hyperthermia

2000

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“…Researchers found an abnormality in the sodium channel, caused by chromosome 17, in 75% of MHS South African families in North America who did not exhibit abnormalities in chromosome 19. 98 This hypothesis received further support the same year, which termed the new finding MHS2, but an established cause for MH has not been shown. 99 In 1994, an abnormality in chromosome 7 was identified in MHS individuals who lacked MHS1 and MHS2 expressions.…”

Section: Phosphorous Magnetic Resonance Spectroscopymentioning

confidence: 91%

Scientific Advances in the Genetic Understanding and Diagnosis of Malignant Hyperthermia

Hernandez¹,

Secrest²,

Hill³

et al. 2009

Journal of PeriAnesthesia Nursing

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“…In contrast to these genome-wide analyses in which large pedigrees were studied, a number of relatively small MH families for which linkage to the ryanodine receptor gene on chromosome 19 was excluded were tested in a candidate-gene approach. The first alternative locus was assigned to chromosome 17q11.2-q24, which suggested SCN4A, the gene encoding the skeletal muscle sodium channel, as candidate gene (96,97). Apparently some of the families had a muscle Na + channelopathy (98,99), which could explain the anesthesia-related events as exaggerated myotonic reactions.…”

Section: Genetic Linkage Studies Within Familiesmentioning

confidence: 99%

Muscle channelopathies and critical points in functional and genetic studies

Jurkat‐Rott

Lehmann‐Horn²

2005

Journal of Clinical Investigation

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Muscle channelopathies are caused by mutations in ion channel genes, by antibodies directed against ion channel proteins, or by changes of cell homeostasis leading to aberrant splicing of ion channel RNA or to disturbances of modification and localization of channel proteins. As ion channels constitute one of the only protein families that allow functional examination on the molecular level, expression studies of putative mutations have become standard in confirming that the mutations cause disease. Functional changes may not necessarily prove disease causality of a putative mutation but could be brought about by a polymorphism instead. These problems are addressed, and a more critical evaluation of the underlying genetic data is proposed.

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Adult muscle sodium channel α-subunit is a gene candidate for malignant hyperthermia susceptibility

Cited by 42 publications

References 15 publications

Genetics and pathogenesis of malignant hyperthermia

Genetics and pathogenesis of malignant hyperthermia

Scientific Advances in the Genetic Understanding and Diagnosis of Malignant Hyperthermia

Muscle channelopathies and critical points in functional and genetic studies

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