Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A. SCN5A mutations associated with overlap phenotype of long QT syndrome type 3 and Brugada syndrome.

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Standard

Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A. SCN5A mutations associated with overlap phenotype of long QT syndrome type 3 and Brugada syndrome. / Kanters, Jørgen K.; Yuan, Lei; Hedley, Paula L; Stoevring, Birgitte; Jons, Christian; Bloch Thomsen, Poul Erik; Grunnet, Morten; Christiansen, Michael; Jespersen, Thomas.

I: Circulation Journal, Bind 78, Nr. 5, 06.03.2014, s. 1136-43.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Kanters, JK, Yuan, L, Hedley, PL, Stoevring, B, Jons, C, Bloch Thomsen, PE, Grunnet, M, Christiansen, M & Jespersen, T 2014, 'Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A. SCN5A mutations associated with overlap phenotype of long QT syndrome type 3 and Brugada syndrome.', Circulation Journal, bind 78, nr. 5, s. 1136-43. https://doi.org/10.1253/circj.CJ-13-1167

APA

Kanters, J. K., Yuan, L., Hedley, P. L., Stoevring, B., Jons, C., Bloch Thomsen, P. E., Grunnet, M., Christiansen, M., & Jespersen, T. (2014). Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A. SCN5A mutations associated with overlap phenotype of long QT syndrome type 3 and Brugada syndrome. Circulation Journal, 78(5), 1136-43. https://doi.org/10.1253/circj.CJ-13-1167

Vancouver

Kanters JK, Yuan L, Hedley PL, Stoevring B, Jons C, Bloch Thomsen PE o.a. Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A. SCN5A mutations associated with overlap phenotype of long QT syndrome type 3 and Brugada syndrome. Circulation Journal. 2014 mar. 6;78(5):1136-43. https://doi.org/10.1253/circj.CJ-13-1167

Author

Kanters, Jørgen K. ; Yuan, Lei ; Hedley, Paula L ; Stoevring, Birgitte ; Jons, Christian ; Bloch Thomsen, Poul Erik ; Grunnet, Morten ; Christiansen, Michael ; Jespersen, Thomas. / Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A. SCN5A mutations associated with overlap phenotype of long QT syndrome type 3 and Brugada syndrome. I: Circulation Journal. 2014 ; Bind 78, Nr. 5. s. 1136-43.

Bibtex

@article{87ebd321b50845c39e361057499bd943,
title = "Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A.: SCN5A mutations associated with overlap phenotype of long QT syndrome type 3 and Brugada syndrome.",
abstract = "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 (I(Na,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.",
author = "Kanters, {J{\o}rgen K.} and Lei Yuan and Hedley, {Paula L} and Birgitte Stoevring and Christian Jons and {Bloch Thomsen}, {Poul Erik} and Morten Grunnet and Michael Christiansen and Thomas Jespersen",
year = "2014",
month = mar,
day = "6",
doi = "10.1253/circj.CJ-13-1167",
language = "English",
volume = "78",
pages = "1136--43",
journal = "Circulation Journal",
issn = "1346-9843",
publisher = "Japanese Circulation Society",
number = "5",

}

RIS

TY - JOUR

T1 - Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A.

T2 - SCN5A mutations associated with overlap phenotype of long QT syndrome type 3 and Brugada syndrome.

AU - Kanters, Jørgen K.

AU - Yuan, Lei

AU - Hedley, Paula L

AU - Stoevring, Birgitte

AU - Jons, Christian

AU - Bloch Thomsen, Poul Erik

AU - Grunnet, Morten

AU - Christiansen, Michael

AU - Jespersen, Thomas

PY - 2014/3/6

Y1 - 2014/3/6

N2 - 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 (I(Na,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.

AB - 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 (I(Na,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.

U2 - 10.1253/circj.CJ-13-1167

DO - 10.1253/circj.CJ-13-1167

M3 - Journal article

C2 - 24599044

VL - 78

SP - 1136

EP - 1143

JO - Circulation Journal

JF - Circulation Journal

SN - 1346-9843

IS - 5

ER -

ID: 113691598