1500 del K
(mixed phenotype: LQT3, BrS, CCD)

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N.S. : non different from WT

COMMENTS and CLINICAL FINDINGS
In this study the authors describe a four-generation family presenting with a complex phenotype with sudden death and features resembling long QT syndrome, Brugada syndrome, and conduction system disease at the same time.

Closed-state inactivation rate was enhanced more than tenfold, resulting in a marked reduction of Na+ channel availability at the normal resting potential of cardiac cells. Open-state inactivation rate was also increased, but to a lesser extent. The reduction of the Na+ current was sufficient to account for the Brugada syndrome and the conduction disturbance The late component of Na+ current resulting from a return from the inactivated state is increased almost threefold in the K1500. This late component of Na+ current would prolong the action potential duration and the QT interval.

During trains of 100-ms pulses (cycle length 150 ms) no use-dependent reduction of INa was observed. suggesting that recovery from inactivation must be extremely rapid in the K1500 mutant channel.

Single-channel current amplitude was similar in the two channel types (1.4 ± 0.1 and 1.55 ± 0.05 pA; n = 4 for both hH1 and K1500). However, the mean open time was significantly reduced in the K1500 mutant (0.66 ± 0.02 ms in the wild-type vs. 0.56 ± 0.03 ms in the K1500 mutant P < 0.05). Furthermore, isolated brief openings as well as bursts of openings were also evident