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GENATLAS PHENOTYPE

last update : 4/04/08

Symbol	CCO
Location	19q13.2
Name	central core disease of muscle
Other name(s)	nemaline rod myopathy
Corresponding gene	RYR1
Other symbol(s)	CCD
Main clinical features	characterized by hypotonia and proximal muscle weakness in infancy, leading to the delay of motor milestones, with a variable severity of symptoms, a low progressive course associated skeletal defects and microscopically amorphous-looking areas (cores) in the predominant type I fibers also presenting as a severe form associated to malignant hyperthermia susceptibility
Genetic determination	autosomal dominant
	autosomal recessive
Prevalence	more than 90% of patients with central core disease
Related entries	including cases of centronuclear myopathy (Jungbluth 2007)
Function/system disorder	neuromuscular
Type	disease

Gene product

Name	ryanodine receptor, calcium release channel (RYR1)

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments
missense		abnormal protein/loss of function	mostly missense mutations clustered in the myoplastic domain, clustering in exons 101 and 102 and altering calcium homeostasis (reduce the Ca2+ sensitivity and amplitude of Ca2+-dependent Ca2+ release)
deletion			reduce Ca(2+) release following RYR1 activation

Remark(s)

Genotype/Phenotype correlations

patients with C-terminal mutations had earlier onset and rather consistent muscle pathology characterized by the presence of distinct cores in almost all type 1 fibres, interstitial fibrosis and type 2 fibre deficiency in contrast, patients with mutations outside the C-terminal region had milder clinical phenotype and harbour more atypical cores in their muscle fibres