Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disease with autosomal dominant inheritance triggered by exposure to commonly used inhalational anaesthetics or depolarising muscle relaxants. A MHS locus has been identified on human chromosome 19q12-q13.2 and the gene for the skeletal muscle calcium release channel of sarcoplasmic reticulum (ryanodine receptor) (RYR1) is considered a candidate for the molecular defect. However, MH has been shown to be genetically heterogeneous, and in the ensuing search for other MHS genes, a locus on chromosome 17q has been proposed, and the gene for the adult muscle sodium channel (SCN4A) was suggested as a candidate. We performed linkage studies using polymorphic microsatellite markers for subunits of the skeletal muscle dihydropyridine (DHP) receptor, CACNL1A3 mapped to chromosome 1q, as well as C-ACNLB1 and CACNLG, the latter two localised on chromosome 17q11.2-q24 in proximity to the proposed MHS2 and the SCN4A loci, and we also included markers for the loci D17S250, D17S579, NM23 (NME1), GH1, and SCN4A from that region. Our results exclude the alpha 1, beta 1 and gamma subunit of the DHP receptor as well as the SCN4A locus from that region. Our results exclude the alpha 1, beta 1, and gamma subunit of the DHP receptor as well as the SCN4A locus as candidates for the molecular defect in MHS for these pedigrees where also the RYR1 on chromosome 19q13.1 has been excluded. A multipoint analysis excludes the disease from the entire 84 cM interval containing the proposed MHS locus on chromosome 17q.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exclusion of malignant hyperthermia susceptibility (MHS) from a putative MHS2 locus on chromosome 17q and of the alpha 1, beta 1, and gamma subunits of the dihydropyridine receptor calcium channel as candidates for the molecular defect. 839 39

Malignant hyperthermia susceptibility (MHS) is an autosomal dominant disorder of skeletal muscle which manifests as a life-threatening hypermetabolic crisis triggered by commonly-used inhalation anaesthetics and depolarizing muscle relaxants. Defects in the ryanodine receptor (RYR1) protein have been proposed to underly MHS, but significant genetic heterogeneity in MHS has recently been demonstrated. In order to investigate the potential roles played by other skeletal muscle calcium channels in MHS, we isolated cosmids containing the gene encoding the beta 1-subunit of skeletal muscle L-type voltage-dependent calcium channel (CACNLB1). We identified a new, highly polymorphic dinucleotide repeat motif close to this gene, and linkage analysis placed the marker proximal to the HOX2B locus, previously localized to chromosome segment 17q21-q22. We recently identified a novel marker within the gamma-subunit locus (CACNLG) at band 17q24, and since both markers are within the 17q11.2-q24 region reported to contain the MHS2 locus, we tested them for linkage in MHS families whose disease trait has been shown not to co-segregate with markers for the RYR1 region on chromosome 19q13.1. Our results exclude CACNLB1 and CACNLG as candidate genes for MHS2, and do not support the reported chromosome 17q localization for the MHS2 locus in our families.
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PMID:Genetic mapping of the beta 1- and gamma-subunits of the human skeletal muscle L-type voltage-dependent calcium channel on chromosome 17q and exclusion as candidate genes for malignant hyperthermia susceptibility. 839 40