Flecainide Provocation Reveals Concealed Brugada Syndrome in a Long QT Syndrome Family With a Novel L1786Q Mutation in SCN5A

被引:22
作者
Kanters, Jorgen K. [1 ,2 ]
Yuan, Lei [1 ]
Hedley, Paula L. [3 ,5 ]
Stoevring, Birgitte [3 ]
Jons, Christian [2 ]
Thomsen, Poul Erik Bloch [2 ]
Grunnet, Morten [1 ,4 ]
Christiansen, Michael [3 ]
Jespersen, Thomas [1 ]
机构
[1] Danish Natl Fdn Res Ctr Arrhythmias DARC, Lab Expt Cardiol, Dept Biomed Sci, Copenhagen, Denmark
[2] Gentofte Univ Hosp, Dept Cardiol P, Copenhagen, Denmark
[3] Statens Serum Inst, DK-2300 Copenhagen, Denmark
[4] NeuroSearch, Ballerup, Denmark
[5] Univ Stellenbosch, Dept Biomed Sci, Cape Town, South Africa
基金
新加坡国家研究基金会;
关键词
Ion channel kinetics; Repolarization; Sodium channel blockade; T-wave morphology; ST SEGMENT ELEVATION; CAPILLARY-ELECTROPHORESIS; CHANNEL; KCNE1; KCNQ1; GENE; POLYMORPHISMS; ASSOCIATION; PHENOTYPE; SPECTRUM;
D O I
10.1253/circj.CJ-13-1167
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Mutations in SCN5A can result in both long QT type 3 (LQT3) and Brugada syndrome (BrS), and a few mutations have been found to have an overlapping phenotype. Long QT syndrome is characterized by prolonged QT interval, and a prerequisite for a BrS diagnosis is ST elevation in the right precordial leads of the electrocardiogram. Methods and Results: In a Danish family suffering from long QT syndrome, a novel missense mutation in SCN5A, changing a leucine residue into a glutamine residue at position 1786 (L1786Q), was found to be present in heterozygous form co-segregating with prolonged QT interval. The proband presented with an aborted cardiac arrest, and his mother died suddenly and unexpectedly at the age of 65. Flecainide treatment revealed coved ST elevation in all mutation carriers. Electrophysiological investigations of the mutant in HEK293 cells indicated a reduced peak current, a negative shift in inactivation properties and a positive shift in activation properties, compatible with BrS. Furthermore, the sustained (INa, late) tetrodotoxin-sensitive sodium current was found to be drastically increased, explaining the association between the mutation and LQT syndrome. Conclusions: The L1786Q mutation is associated with a combined LQT3 and concealed BrS phenotype explained by gating characteristics of the mutated ion channel protein. Hence, sodium channel blockade should be considered in clinical evaluation of apparent LQT3 patients.
引用
收藏
页码:1136 / 1143
页数:8
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