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ca++ ed autismo


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ca++ ed autismo

ca++ ed autismo (1)

Correlazioni fra alterazione dei canali del calcio ed autismo.

I profondi cambiamenti biomolecolari provocano un lento deterioramento del normale sviluppo cerebrale con apoptosi e perdita di competenze cognitive integrative e sociali.

 

Abstract

CaV1.2, the cardiac L-type calcium channel, is important for excitation and contraction of the heart. Its role in other tissues is unclear. Here we present Timothy syndrome, a novel disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism. In every case, Timothy syndrome results from the identical, de novo CaV1.2 missense mutation G406R. CaV1.2 is expressed in all affected tissues. Functional expression reveals that G406R produces maintained inward Ca2+ currents by causing nearly complete loss of voltage-dependent channel inactivation. This likely induces intracellular Ca2+ overload in multiple cell types. In the heart, prolonged Ca2+ current delays cardiomyocyte repolarization and increases risk of arrhythmia, the ultimate cause of death in this disorder. These discoveries establish the importance of CaV1.2 in human physiology and development and implicate Ca2+ signaling in autism.

 

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