A CACNA1C Mutation that Causes a Subset of Timothy Syndrome Phenotypes Correlates.
Timothy syndrome (TS) is a rare congenital long QT syndrome (LQTS) associated with extracardiac manifestations including craniofacial dysmorphia and dental abnormalities. The locus for TS is CACNA1C, which encodes the CaV1.2 L-type Ca(2+) channel, for which canonical mutations lead to a decrease in voltage-dependent inactivation (VDI). However, a recent report of a patient with LQTS in isolation and a CACNA1C mutation that did not affect VDI raised the question whether altered VDI is necessary for extracardiac phenotypes. In a patient with a maternally inherited microdeletion with a chromosomal translocation who presented with LQTS and associated ventricular tachyarrhythmias (Figure A), a subset of TS phenotypes, and a skeletal myopathy not readily explained by the translocation, we sought to identify a causative mutation for the TS phenotypes.
Hennessey, JA; Jiang, Y; Miller, JD; Stadt, HA; Patrick, W; Pfeiffer, R; Antzelevitch, C; Kanter, R; Pitt, GS
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