Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na
v
1.5 and K
v
4.3 channel currents
Heart Rhythm, Volume 9, No. 5, Year 2012
Notification
URL copied to clipboard!
Description
BACKGROUND: Cardiac sodium channel β-subunit mutations have been associated with several inherited cardiac arrhythmia syndromes. OBJECTIVE: To identify and characterize variations in SCN1Bb associated with Brugada syndrome (BrS) and sudden infant death syndrome (SIDS). METHODS: All known exons and intron borders of the BrS-susceptibility genes were amplified and sequenced in both directions. Wild type (WT) and mutant genes were expressed in TSA201 cells and studied using co-immunoprecipitation and whole-cell patch-clamp techniques. RESULTS: Patient 1 was a 44-year-old man with an ajmaline-induced type 1 ST-segment elevation in V1 and V2 supporting the diagnosis of BrS. Patient 2 was a 62-year-old woman displaying a coved-type BrS electrocardiogram who developed cardiac arrest during fever. Patient 3 was a 4-month-old female SIDS case. A R214Q variant was detected in exon 3A of SCN1Bb (Nav1B) in all three probands, but not in any other gene previously associated with BrS or SIDS. R214Q was identified in 4 of 807 ethnically-matched healthy controls (0.50%). Co-expression of SCN5A/WT + SCN1Bb/R214Q resulted in peak sodium channel current (INa) 56.5% smaller compared to SCN5A/WT + SCN1Bb/WT (n = 11-12, P<0.05). Co-expression of KCND3/WT + SCN1Bb/R214Q induced a Kv4.3 current (transient outward potassium current, Ito) 70.6% greater compared with KCND3/WT + SCN1Bb/WT (n = 10-11, P<0.01). Co-immunoprecipitation indicated structural association between Navβ1B and Na v1.5 and Kv4.3. CONCLUSION: Our results suggest that R214Q variation in SCN1Bb is a functional polymorphism that may serve as a modifier of the substrate responsible for BrS or SIDS phenotypes via a combined loss of function of sodium channel current and gain of function of transient outward potassium current. © 2012 Heart Rhythm Society.
Authors & Co-Authors
Hu, Dan
United States, Utica
Masonic Medical Research Laboratory
Barajas-Martínez, Héctor M.
United States, Utica
Masonic Medical Research Laboratory
Medeiros-Domingo, Argelia
United States, Rochester
Mayo Clinic
CROTTI, L.
Italy, Pavia
Università Degli Studi Di Pavia
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Italy, Pavia
Fondazione Irccs Policlinico San Matteo
Veltmann, Christian
Germany, Mannheim
Universitätsklinikum Mannheim
Schimpf, Rainer
Germany, Mannheim
Universitätsklinikum Mannheim
Urrutia, Janire
Spain, Leioa
Universidad Del Pais Vasco
Alday, Aintzane
Spain, Leioa
Universidad Del Pais Vasco
Casis, Oscar
Spain, Leioa
Universidad Del Pais Vasco
Pfeiffer, Ryan D.
United States, Utica
Masonic Medical Research Laboratory
Burashnikov, Elena
United States, Utica
Masonic Medical Research Laboratory
Cáceres, Gabriel
United States, Utica
Masonic Medical Research Laboratory
Tester, David J.
United States, Rochester
Mayo Clinic
Wolpert, Christian
Germany, Ludwigsburg
Kliniken Ludwigsburg Bietigheim Ggmbh
Borggrefe, Martin M.
Germany, Mannheim
Universitätsklinikum Mannheim
Schwartz, Peter J.
Italy, Pavia
Università Degli Studi Di Pavia
Italy, Pavia
Fondazione Irccs Policlinico San Matteo
Italy, Milan
Irccs Istituto Auxologico Italiano
South Africa, Cape Town
University of Cape Town
South Africa, Stellenbosch
Stellenbosch University
Saudi Arabia, Riyadh
College of Medicine
Ackerman, Michael John
United States, Rochester
Mayo Clinic
Antzelevitch, Charles
United States, Utica
Masonic Medical Research Laboratory
Statistics
Citations: 105
Authors: 18
Affiliations: 12
Identifiers
Doi:
10.1016/j.hrthm.2011.12.006
ISSN:
15475271
e-ISSN:
15563871
Research Areas
Genetics And Genomics
Health System And Policy
Maternal And Child Health
Noncommunicable Diseases
Participants Gender
Female