Mutations in sodium channel beta1- and beta2-subunits associated with atrial fibrillation. Watanabe, H., Darbar, D., Kaiser, D., Jiramongkolchai, K., Chopra, S., Donahue, B., Kannankeril, P., & Roden, D. Circ Arrhythm Electrophysiol, 2(3):268–275, Jun, 2009. bibtex @Article{RSM:Wat2009,
author = "H. Watanabe and D. Darbar and D.W. Kaiser and K.
Jiramongkolchai and S. Chopra and B.S. Donahue and P.J.
Kannankeril and D.M. Roden",
title = "Mutations in sodium channel beta1- and beta2-subunits
associated with atrial fibrillation.",
journal = "Circ Arrhythm Electrophysiol",
year = "2009",
month = "Jun",
volume = "2",
number = "3",
pages = "268--275",
robnote = "BACKGROUND: We and others have reported mutations in the
cardiac predominant sodium channel gene SCN5A in patients
with atrial fibrillation (AF). We also have reported that
SCN1B is associated with Brugada syndrome and isolated
cardiac conduction disease. We tested the hypothesis that
mutations in the 4 sodium channel beta-subunit genes
SCN1B-SCN4B contribute to AF susceptibility. METHODS AND
RESULTS: Screening for mutations in the 4 beta-subunit
genes was performed in 480 patients with AF (118 patients
with lone AF and 362 patients with AF and cardiovascular
disease) and 548 control subjects (188 ethnically defined
anonymized subjects and 360 subjects without AF). The
effects of mutant beta-subunits on SCN5A mediated currents
were studied using electrophysiological studies. We
identified 2 nonsynonymous variants in SCN1B (resulting in
R85H, D153N) and 2 in SCN2B (R28Q, R28W) in patients with
AF. These occur at residues highly conserved across
mammals and were absent in control subjects. In 3 of 4
mutation carriers, the ECGs showed saddleback-type
ST-segment elevation in the right precordial leads.
Transcripts encoding both SCN1B and SCN2B were detected in
human atrium and ventricle. In heterologous expression
studies using Chinese hamster ovary cells, the mutant
beta1- or beta2-subunits reduced SCN5A-mediated current
and altered channel gating compared with coexpression of
wild-type subunits. CONCLUSIONS: Loss of function
mutations in sodium channel beta-subunits were identified
in patients with AF and were associated with a distinctive
ECG phenotype. These findings further support the
hypothesis that decreased sodium current enhances AF
susceptibility.",
bibdate = "Mon Dec 7 22:15:47 2009",
pmcid = "2010/06/01 PHST- 2009/03/06 [aheadofprint]",
}
Downloads: 0
{"_id":"pSWXz7roEyHgni7cb","bibbaseid":"watanabe-darbar-kaiser-jiramongkolchai-chopra-donahue-kannankeril-roden-mutationsinsodiumchannelbeta1andbeta2subunitsassociatedwithatrialfibrillation-2009","downloads":0,"creationDate":"2016-07-01T21:38:42.748Z","title":"Mutations in sodium channel beta1- and beta2-subunits associated with atrial fibrillation.","author_short":["Watanabe, H.","Darbar, D.","Kaiser, D.","Jiramongkolchai, K.","Chopra, S.","Donahue, B.","Kannankeril, P.","Roden, D."],"year":2009,"bibtype":"article","biburl":"http://www.sci.utah.edu/~macleod/Bibtex/biglit.bib","bibdata":{"bibtype":"article","type":"article","author":[{"firstnames":["H."],"propositions":[],"lastnames":["Watanabe"],"suffixes":[]},{"firstnames":["D."],"propositions":[],"lastnames":["Darbar"],"suffixes":[]},{"firstnames":["D.W."],"propositions":[],"lastnames":["Kaiser"],"suffixes":[]},{"firstnames":["K."],"propositions":[],"lastnames":["Jiramongkolchai"],"suffixes":[]},{"firstnames":["S."],"propositions":[],"lastnames":["Chopra"],"suffixes":[]},{"firstnames":["B.S."],"propositions":[],"lastnames":["Donahue"],"suffixes":[]},{"firstnames":["P.J."],"propositions":[],"lastnames":["Kannankeril"],"suffixes":[]},{"firstnames":["D.M."],"propositions":[],"lastnames":["Roden"],"suffixes":[]}],"title":"Mutations in sodium channel beta1- and beta2-subunits associated with atrial fibrillation.","journal":"Circ Arrhythm Electrophysiol","year":"2009","month":"Jun","volume":"2","number":"3","pages":"268–275","robnote":"BACKGROUND: We and others have reported mutations in the cardiac predominant sodium channel gene SCN5A in patients with atrial fibrillation (AF). We also have reported that SCN1B is associated with Brugada syndrome and isolated cardiac conduction disease. We tested the hypothesis that mutations in the 4 sodium channel beta-subunit genes SCN1B-SCN4B contribute to AF susceptibility. METHODS AND RESULTS: Screening for mutations in the 4 beta-subunit genes was performed in 480 patients with AF (118 patients with lone AF and 362 patients with AF and cardiovascular disease) and 548 control subjects (188 ethnically defined anonymized subjects and 360 subjects without AF). The effects of mutant beta-subunits on SCN5A mediated currents were studied using electrophysiological studies. We identified 2 nonsynonymous variants in SCN1B (resulting in R85H, D153N) and 2 in SCN2B (R28Q, R28W) in patients with AF. These occur at residues highly conserved across mammals and were absent in control subjects. In 3 of 4 mutation carriers, the ECGs showed saddleback-type ST-segment elevation in the right precordial leads. Transcripts encoding both SCN1B and SCN2B were detected in human atrium and ventricle. In heterologous expression studies using Chinese hamster ovary cells, the mutant beta1- or beta2-subunits reduced SCN5A-mediated current and altered channel gating compared with coexpression of wild-type subunits. CONCLUSIONS: Loss of function mutations in sodium channel beta-subunits were identified in patients with AF and were associated with a distinctive ECG phenotype. These findings further support the hypothesis that decreased sodium current enhances AF susceptibility.","bibdate":"Mon Dec 7 22:15:47 2009","pmcid":"2010/06/01 PHST- 2009/03/06 [aheadofprint]","bibtex":"@Article{RSM:Wat2009,\n author = \"H. Watanabe and D. Darbar and D.W. Kaiser and K.\n Jiramongkolchai and S. Chopra and B.S. Donahue and P.J.\n Kannankeril and D.M. Roden\",\n title = \"Mutations in sodium channel beta1- and beta2-subunits\n associated with atrial fibrillation.\",\n journal = \"Circ Arrhythm Electrophysiol\",\n year = \"2009\",\n month = \"Jun\",\n volume = \"2\",\n number = \"3\",\n pages = \"268--275\",\n robnote = \"BACKGROUND: We and others have reported mutations in the\n cardiac predominant sodium channel gene SCN5A in patients\n with atrial fibrillation (AF). We also have reported that\n SCN1B is associated with Brugada syndrome and isolated\n cardiac conduction disease. We tested the hypothesis that\n mutations in the 4 sodium channel beta-subunit genes\n SCN1B-SCN4B contribute to AF susceptibility. METHODS AND\n RESULTS: Screening for mutations in the 4 beta-subunit\n genes was performed in 480 patients with AF (118 patients\n with lone AF and 362 patients with AF and cardiovascular\n disease) and 548 control subjects (188 ethnically defined\n anonymized subjects and 360 subjects without AF). The\n effects of mutant beta-subunits on SCN5A mediated currents\n were studied using electrophysiological studies. We\n identified 2 nonsynonymous variants in SCN1B (resulting in\n R85H, D153N) and 2 in SCN2B (R28Q, R28W) in patients with\n AF. These occur at residues highly conserved across\n mammals and were absent in control subjects. In 3 of 4\n mutation carriers, the ECGs showed saddleback-type\n ST-segment elevation in the right precordial leads.\n Transcripts encoding both SCN1B and SCN2B were detected in\n human atrium and ventricle. In heterologous expression\n studies using Chinese hamster ovary cells, the mutant\n beta1- or beta2-subunits reduced SCN5A-mediated current\n and altered channel gating compared with coexpression of\n wild-type subunits. CONCLUSIONS: Loss of function\n mutations in sodium channel beta-subunits were identified\n in patients with AF and were associated with a distinctive\n ECG phenotype. These findings further support the\n hypothesis that decreased sodium current enhances AF\n susceptibility.\",\n bibdate = \"Mon Dec 7 22:15:47 2009\",\n pmcid = \"2010/06/01 PHST- 2009/03/06 [aheadofprint]\",\n}\n\n","author_short":["Watanabe, H.","Darbar, D.","Kaiser, D.","Jiramongkolchai, K.","Chopra, S.","Donahue, B.","Kannankeril, P.","Roden, D."],"key":"RSM:Wat2009","id":"RSM:Wat2009","bibbaseid":"watanabe-darbar-kaiser-jiramongkolchai-chopra-donahue-kannankeril-roden-mutationsinsodiumchannelbeta1andbeta2subunitsassociatedwithatrialfibrillation-2009","role":"author","urls":{},"metadata":{"authorlinks":{}},"downloads":0,"html":""},"search_terms":["mutations","sodium","channel","beta1","beta2","subunits","associated","atrial","fibrillation","watanabe","darbar","kaiser","jiramongkolchai","chopra","donahue","kannankeril","roden"],"keywords":[],"authorIDs":[],"dataSources":["5HG3Kp8zRwDd7FotB"]}