Disease relevance of Myopathy, Central Core

• Similarities between the mutations identified in the RyR2 gene and those found in the gene RyR1 that cause malignant hyperthermia and central core disease are discussed [1].
• The ryanodine receptor (RYR1) is mutated in a number of MH pedigrees, some members of which also have central core disease (CCD), an inherited myopathy closely associated with MH [2].
• We describe the presence of microtubule-associated protein tau epitopes in various muscle fiber lesions in oculopharyngeal and Becker muscular dystrophy, dermatomyositis, central core disease, neurogenic atrophy, and in the recovery phase of an attack of malignant hyperthermia [3].
• Muscle fibers strongly reactive for both adenosinetriphosphatase and nicotinamide-adenine dinucleotide diaphorase, observed in central core disease and mitochondrial myopathy, were not associated with increased terminal innervation ratio [4].
• Skeletal-muscle pathology can be caused by mutations in ryanodine receptors (malignant hyperthermia, porcine stress syndrome, central-core disease), dihydropyridine receptors (familial hypokalemic periodic paralysis, malignant hyperthermia, muscular dysgenesis) or Ca(2+)pumps (Brody disease) [5].

High impact information on Myopathy, Central Core

• A mutation in the human ryanodine receptor gene associated with central core disease [6].
• Excitation--contraction uncoupling by a human central core disease mutation in the ryanodine receptor [7].
• Missense mutations in the beta-myosin heavy-chain gene cause central core disease in hypertrophic cardiomyopathy [8].
• We studied seven patients (fetuses/infants) from six unrelated families affected by central core disease (CCD) and presenting with a fetal akinesia syndrome [9].
• Caffeine and halothane sensitivity of intracellular Ca2+ release is altered by 15 calcium release channel (ryanodine receptor) mutations associated with malignant hyperthermia and/or central core disease [10].

Chemical compound and disease context of Myopathy, Central Core

• A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease [11].
• All mutants except I4829A and I4829T (corresponding to the I4897T central core disease mutant in RyR1) displayed caffeine-induced Ca(2+) release in HEK-293 cells; only mutants G4826A, I4829V, and G4830A retained high affinity [(3)H]ryanodine binding; and single-channel function was found for all mutants tested, except for G4822A and A4825V [12].
• Patients with central core disease appear to be more susceptible to MH; possibly those with elevated serum creatine phosphokinase levels, as in our patient, are especially susceptible [13].
• Prophylactic use of dantrolene in a patient with central core disease [14].
• Muscle fructose 1,6-diphosphatase deficiency associated with an atypical central core disease [15].

Biological context of Myopathy, Central Core

• In a large kindred in which the gene for CCO is segregating, two-point linkage analysis gave a maximum lod score, between the central core disease locus (CCO) and the ryanodine receptor locus (RYR1), of 11.8, with no recombination [16].
• Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis [17].
• BACKGROUND: The search for novel mutations in the ryanodine receptor subtype 1 (RYR1) gene causing malignant hyperthermia and central core disease is hampered by the fact that the gene contains 106 exons [18].
• Haplotype analysis using chromosome 19q markers indicated that the three families are likely to be unrelated, providing confirmation that the MH/central core disease region 1 of RYR1 is a mutation hot spot [19].
• In skeletal muscle, malignant hyperthermia and central core disease result from point mutations in RYR1, the skeletal isoform of RyRs [20].

Anatomical context of Myopathy, Central Core

• Malignant hyperthermia (MH) and central core disease (CCD) are autosomal dominant disorders of skeletal muscle in which a potentially fatal hypermetabolic crisis can be triggered by commonly used anesthetic agents [10].

Gene context of Myopathy, Central Core

• The 800-kb contig of cloned reagents will facilitate the detailed characterization of the RYR1 gene and other loci that may be closely related to central core disease [21].
• A prominent myotilin immunostaining of nemaline rods and core lesions was detected in all ten cases of nemaline myopathy and five cases of central core disease [22].
• Does the A3333G mutation in the CACNL1A3 gene, detected in malignant hyperthermia, also occur in central core disease [23]?
• Instead we identified homologs of human genes that are autosomally localized: the ryanodine receptor type I (RYRI), which is implicated in malignant hyperthermia and central core disease, and the HE6 gene [24].
• Marker D19S9 (p1J2) was linked to central core disease with a lod score of 6.4 at theta = 0.03 (support interval 0.01-0.14) thus localizing the gene for this disorder in or very close to 19q12-q13.2 [25].

References