Central Core Disease—an Investigation of a Rare Muscle Cell Abnormality

Engel, W. King; Foster, John Burt; Hughes, B.R.; Huxley, H. E.; Mahler, Robert

doi:10.1093/brain/84.2.167

Cited by 106 publications

(33 citation statements)

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“…EM of cores in biopsies from CCD patients reveals a wide variety of structural alterations affecting the contractile elements, SR, and transverse tubules (T-tubules) (7)(8)(9)(10)(11). Cores vary in the degree of damage/disruption to the myofibrils, including heavily contracted regions (contracture cores), disorganized and damaged regions (structured cores), and regions lacking contractile filaments (unstructured cores) (11,12).…”

mentioning

confidence: 99%

Characterization and temporal development of cores in a mouse model of malignant hyperthermia

Boncompagni

Rossi

Micaroni

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

100

127

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Malignant hyperthermia (MH) and central core disease are related skeletal muscle diseases often linked to mutations in the type 1 ryanodine receptor (RYR1) gene, encoding for the Ca 2؉ release channel of the sarcoplasmic reticulum (SR). In humans, the Y522S RYR1 mutation is associated with malignant hyperthermia susceptibility (MHS) and the presence in skeletal muscle fibers of core regions that lack mitochondria. In heterozygous Y522S knock-in mice (RYR1 Y522S/WT ), the mutation causes SR Ca 2؉ leak and MHS. Here, we identified mitochondrial-deficient core regions in skeletal muscle fibers from RYR1 Y522S/WT knock-in mice and characterized the structural and temporal aspects involved in their formation. Mitochondrial swelling/disruption, the initial detectable structural change observed in young-adult RYR1 Y522S/WT mice (2 months), does not occur randomly but rather is confined to discrete areas termed presumptive cores. This localized mitochondrial damage is followed by local disruption/loss of nearby SR and transverse tubules, resulting in early cores (2-4 months) and small contracture cores characterized by extreme sarcomere shortening and lack of mitochondria. At later stages (1 year), contracture cores are extended, frequent, and accompanied by areas in which contractile elements are also severely compromised (unstructured cores). Based on these observations, we propose a possible series of events leading to core formation in skeletal muscle fibers of RYR1 Y522S/WT mice: Initial mitochondrial/SR disruption in confined areas causes significant loss of local Ca 2؉ sequestration that eventually results in the formation of contractures and progressive degradation of the contractile elements.central core disease ͉ excitation-contraction coupling ͉ muscle disease ͉ ryanodine receptor ͉ mitochondria

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mentioning

confidence: 99%

Characterization and temporal development of cores in a mouse model of malignant hyperthermia

Boncompagni

Rossi

Micaroni

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

100

127

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“…Central core disease was first described by Shy and Magee (1956). The biochemical aberrations occurring in the skeletal muscle fibres were first described by Engel et al (1961). In addition to histochemistry and electronmicroscopy, we have examined the activities of phosphorylase and succinic dehydrogenase in whole homogenates and, also, actomyosin Mg2 +activated adenosinetriphosphate (ATPase) and calcium uptake and ATP activity of sarcoplasmic reticulum (SR) which are indicators of the functional integrity of the contractile and relaxing systems of the muscle fibre and are also a guide to the changes in fibre type occurring in diseased muscle.…”

mentioning

confidence: 99%

Central core disease. A correlated genetic, histochemical, ultramicroscopic, and biochemical study.

Isaacs¹,

Heffron²,

Badenhorst³

1975

Journal of Neurology, Neurosurgery & Psychiatry

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SYNOPSIS Two patients suffering from central core disease are presented. The condition is associated with musculoskeletal abnormalities which have been traced back over five generations. In addition to the typical histochemical findings, electronmicroscopic study has revealed the presence of both structured and non-structured cores in adjacent areas. The calcium uptake by the sarcoplasmic reticulum was reduced to one-third of normal. Phosphorylase activity was normal in the one case and reduced to 63% in the other. Actomyosin Mg2 +-activated ATPase activity was decreased, as was the Ca2+-dependent ATPase of the sarcoplasmic reticulum.

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“…Morphologic descriptions of CCD have been quite consistent since the earliest accounts [8,10], Affected fibers are almost exclusively type I. with 2-95% contain ing 1-6 central or eccentric cores. Some variability can be seen from muscle to muscle.…”

Section: Discussionmentioning

confidence: 78%

“…In the current case, no weakness was noted in either parent. Biopsy of unaffected presumed carriers of the condition may show central cores, or may be normal [10].…”

Section: Discussionmentioning

confidence: 99%