Medical Genetics

Understanding Timothy Syndrome

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Science  22 Oct 2004:
Vol. 306, Issue 5696, pp. 579
DOI: 10.1126/science.306.5696.579a

Timothy syndrome is a rare human disorder characterized by diverse physiological and developmental defects, including heart arrythmias, webbing of fingers and toes, and autism. Splawski et al.identify a single mutation in a gene that encodes the calcium channel Cav1.2 as being responsible for the syndrome. The mutation occurs in a highly conserved region that is important for voltage-gated channel inactivation resulting in prolonged influx of calcium into cells. Other calcium channel-based disorders affect distinct organ systems. However, the mutated splice variant of Cav1.2 is widely expressed in tissues and organs, consistent with the scope of disease abnormalities. Mutant channels are sensitive to calcium channel blockers, suggesting the potential use of such drugs in treating this genetic disorder, which is often fatal by 2.5 years of age. The study also suggests that aberrant calcium signaling in the brain may contribute to autism, a condition whose molecular mechanism is not well understood. — LDC

Cell 119, 19 (2004).

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