A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na 1.5 and K 4.3 channel currents
| Autor: | Michael J. Ackerman, Gabriel Caceres, Martin Borggrefe, Charles Antzelevitch, Elena Burashnikov, Lia Crotti, Janire Urrutia, Argelia Medeiros-Domingo, Rainer Schimpf, Hector Barajas-Martinez, Christian Veltmann, David J. Tester, Ryan Pfeiffer, Aintzane Alday, Dan Hu, Christian Wolpert, Oscar Casis, Peter J. Schwartz |
|---|---|
| Přispěvatelé: | Hu, D, Barajas-Martínez, H, Medeiros-Domingo, A, Crotti, L, Veltmann, C, Schimpf, R, Urrutia, J, Alday, A, Casis, O, Pfeiffer, R, Burashnikov, E, Caceres, G, Tester, D, Wolpert, C, Borggrefe, M, Schwartz, P, Ackerman, M, Antzelevitch, C |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Potassium Channels Sudden infant death syndrome Sodium Blotting Western chemistry.chemical_element BIO/18 - GENETICA NAV1.5 Voltage-Gated Sodium Channel Article Electrocardiography SCN1Bb Exon BIO/09 - FISIOLOGIA Physiology (medical) Internal medicine medicine Humans Genetic Predisposition to Disease Brugada syndrome Molecular Biology Polymorphism Genetic business.industry Sodium channel Wild type Infant Arrhythmias Cardiac MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE Middle Aged Voltage-Gated Sodium Channel beta-1 Subunit medicine.disease Potassium channel Endocrinology chemistry Mutation Potassium Female Cardiology and Cardiovascular Medicine business Sudden Infant Death Arrhythmia |
| Zdroj: | Heart Rhythm. 9:760-769 |
| ISSN: | 1547-5271 |
| DOI: | 10.1016/j.hrthm.2011.12.006 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|