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central core disease of muscle (CCD)
Pathology:
1) predominance of type 1 muscle fibers containing amorphous areas (cores)
2) cores do not stain with oxidative & phosphorylase histochemical methods
Genetics:
1) autosomal dominant
2) associated with defects in RyR1 gene
3) coexpression of normal & mutant Thr-4898 RYR1 in a 1:1 ratio, produces RYR1 channels with normal halothane & caffeine sensitivities, but maximal levels of Ca+2 release are reduced by 67%; binding of [3H]ryanodine indicates that the heterozygous channel is activated by Ca+2 concentrations 4-fold lower than normal; single-cell analysis of cotransfected cells shows a significantly increased resting cytoplasmic Ca+2 level & a significantly reduced luminal Ca+2 level; data suggests a leaky channel, possibly caused by a reduction in the Ca+2 concentration required for channel activation; the Thr-4898 mutation gives rise to the severe & penetrant phenotype
5) allelic with malignant hyperthermia [2]
Clinical manifestations:
1) congenital myopathy
2) hypotonia & proximal muscle weakness in infancy
3) delay of motor milestones
4) slow or nonprogressive in adulthood
5) severity of the symptoms may vary from normal to significant muscle weakness
Related
ryanodine receptor 1; RYR-1; RyR1; skeletal muscle-type ryanodine receptor; skeletal muscle Ca+2 release channel (RYR1, RYDR)
General
genetic disease of muscle (inherited myopathy)
Database Correlations
OMIM 117000
References
- OMIM :accession 117000
- Medical Knowledge Self Assessment Program (MKSAP) 19,
American College of Physicians, Philadelphia 2009