SCN5A

Summary

Gene Symbol: SCN5A
Description: sodium channel, voltage gated, type V alpha subunit
Alias: CDCD2, CMD1E, CMPD2, HB1, HB2, HBBD, HH1, ICCD, IVF, LQT3, Nav1.5, PFHB1, SSS1, VF1, cardiac tetrodotoxin-insensitive voltage-dependent sodium channel alpha subunit, sodium channel protein cardiac muscle subunit alpha, sodium channel, voltage-gated, type V, alpha subunit, voltage-gated sodium channel subunit alpha Nav1.5
Species: human

Top Publications

  1. doi SCN5A channelopathies--an update on mutations and mechanisms
    Thomas Zimmer
    Institute of Physiology II, Friedrich Schiller University Jena, Kollegiengasse 9, 07743 Jena, Germany
    Prog Biophys Mol Biol 98:120-36. 2008
  2. doi NaV1.5 Na⁺ channels allosterically regulate the NHE-1 exchanger and promote the activity of breast cancer cell invadopodia
    Lucie Brisson
    INSERM U1069, Nutrition, Croissance et Cancer, Universite Francois Rabelais de Tours, 10 boulevard Tonnelle, 37032 Tours, France
    J Cell Sci 126:4835-42. 2013
  3. ncbi International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels
    William A Catterall
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280
    Pharmacol Rev 57:397-409. 2005
  4. doi Cardiac sodium channel overlap syndromes: different faces of SCN5A mutations
    Carol Ann Remme
    Department of Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Trends Cardiovasc Med 18:78-87. 2008
  5. pmc Genome-wide association study of PR interval
    Arne Pfeufer
    Institute of Human Genetics, Klinikum rechts der Isar der Technischen Universitat Munchen, Munich, Germany
    Nat Genet 42:153-9. 2010
  6. ncbi A sodium-channel mutation causes isolated cardiac conduction disease
    H L Tan
    The Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, The Netherlands
    Nature 409:1043-7. 2001
  7. pmc The sigma-1 receptor binds to the Nav1.5 voltage-gated Na+ channel with 4-fold symmetry
    Dilshan Balasuriya
    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom
    J Biol Chem 287:37021-9. 2012
  8. pmc Mutations in sodium channel β1- and β2-subunits associated with atrial fibrillation
    Hiroshi Watanabe
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 0575, USA
    Circ Arrhythm Electrophysiol 2:268-75. 2009
  9. ncbi Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients
    Aimee D C Paulussen
    Department of Pharmacogenomics, Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, Beerse, Belgium
    J Mol Med (Berl) 82:182-8. 2004
  10. ncbi SCN5A polymorphism restores trafficking of a Brugada syndrome mutation on a separate gene
    Steven Poelzing
    Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Dr, Rammelkamp 658, Cleveland, OH 44109 1998, USA
    Circulation 114:368-76. 2006

Detail Information

Publications235 found, 100 shown here

  1. doi SCN5A channelopathies--an update on mutations and mechanisms
    Thomas Zimmer
    Institute of Physiology II, Friedrich Schiller University Jena, Kollegiengasse 9, 07743 Jena, Germany
    Prog Biophys Mol Biol 98:120-36. 2008
    ..Na(v)1.5, encoded by the SCN5A gene, is the predominant isoform in the heart...
  2. doi NaV1.5 Na⁺ channels allosterically regulate the NHE-1 exchanger and promote the activity of breast cancer cell invadopodia
    Lucie Brisson
    INSERM U1069, Nutrition, Croissance et Cancer, Universite Francois Rabelais de Tours, 10 boulevard Tonnelle, 37032 Tours, France
    J Cell Sci 126:4835-42. 2013
    ..NaV1.5 (also known as SCN5A) Na(+) channels are overexpressed in breast cancer tumours and are associated with metastatic occurrence...
  3. ncbi International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels
    William A Catterall
    Department of Pharmacology, University of Washington, Mailstop 357280, Seattle, WA 98195 7280
    Pharmacol Rev 57:397-409. 2005
    ..This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties...
  4. doi Cardiac sodium channel overlap syndromes: different faces of SCN5A mutations
    Carol Ann Remme
    Department of Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Trends Cardiovasc Med 18:78-87. 2008
    Cardiac sodium channel dysfunction caused by mutations in the SCN5A gene is associated with a number of relatively uncommon arrhythmia syndromes, including long-QT syndrome type 3 (LQT3), Brugada syndrome, conduction disease, sinus node ..
  5. pmc Genome-wide association study of PR interval
    Arne Pfeufer
    Institute of Human Genetics, Klinikum rechts der Isar der Technischen Universitat Munchen, Munich, Germany
    Nat Genet 42:153-9. 2010
    ..At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, ..
  6. ncbi A sodium-channel mutation causes isolated cardiac conduction disease
    H L Tan
    The Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, The Netherlands
    Nature 409:1043-7. 2001
    ..Inherited mutations in SCN5A, the gene encoding the human cardiac sodium (Na+) channel, have been associated with rapid heart rhythms that ..
  7. pmc The sigma-1 receptor binds to the Nav1.5 voltage-gated Na+ channel with 4-fold symmetry
    Dilshan Balasuriya
    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom
    J Biol Chem 287:37021-9. 2012
    ..Interestingly, two known Sig1R ligands, haloperidol and (+)-pentazocine, disrupted the Nav1.5/Sig1R interaction both in vitro and in living cells. Finally, we show that endogenously expressed Sig1R and Nav1.5 also functionally interact...
  8. pmc Mutations in sodium channel β1- and β2-subunits associated with atrial fibrillation
    Hiroshi Watanabe
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 0575, USA
    Circ Arrhythm Electrophysiol 2:268-75. 2009
    We and others have reported mutations in the cardiac predominant sodium channel gene SCN5A in patients with atrial fibrillation (AF)...
  9. ncbi Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients
    Aimee D C Paulussen
    Department of Pharmacogenomics, Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, Beerse, Belgium
    J Mol Med (Berl) 82:182-8. 2004
    ..Five cLQTS genes ( KCNH2, KCNQ1, SCN5A, KCNE1, KCNE2) were thoroughly screened for genetic variations in 32 drug-induced aLQTS patients with confirmed ..
  10. ncbi SCN5A polymorphism restores trafficking of a Brugada syndrome mutation on a separate gene
    Steven Poelzing
    Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Dr, Rammelkamp 658, Cleveland, OH 44109 1998, USA
    Circulation 114:368-76. 2006
    ..Previously, the R282H-SCN5A mutation in the sodium channel gene was identified in patients with Brugada syndrome...
  11. pmc Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test
    Jamie D Kapplinger
    Department of Medicine, Divisions of Cardiovascular Diseases and Pediatric Cardiology, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA
    Heart Rhythm 6:1297-303. 2009
    ..Long QT syndrome (LQTS) is a potentially lethal, highly treatable cardiac channelopathy for which genetic testing has matured from discovery to translation and now clinical implementation...
  12. pmc Solution NMR structure of Apo-calmodulin in complex with the IQ motif of human cardiac sodium channel NaV1.5
    Benjamin Chagot
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA
    J Mol Biol 406:106-19. 2011
    ..The structure also provides insight into the biochemical basis for disease-associated mutations that map to the IQ motif in Na(V)1.5...
  13. doi SCN5A mutations associate with arrhythmic dilated cardiomyopathy and commonly localize to the voltage-sensing mechanism
    William P McNair
    Cardiovascular Institute, University of Colorado Denver, Aurora, Colorado 80045 6511, USA
    J Am Coll Cardiol 57:2160-8. 2011
    The aim of this study was to discern the role of the cardiac voltage-gated sodium ion channel SCN5A in the etiology of dilated cardiomyopathy (DCM).
  14. doi High prevalence of long QT syndrome-associated SCN5A variants in patients with early-onset lone atrial fibrillation
    Morten S Olesen
    Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark
    Circ Cardiovasc Genet 5:450-9. 2012
    ..5, plays a pivotal role in setting the conduction velocity and the initial depolarization of the cardiac myocytes. We hypothesized that early-onset lone AF was associated with genetic variation in SCN5A.
  15. ncbi Novel SCN3B mutation associated with brugada syndrome affects intracellular trafficking and function of Nav1.5
    Taisuke Ishikawa
    Division of Genetic Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
    Circ J 77:959-67. 2013
    ..The major causes of BrS are mutations in SCN5A for a large subunit of the sodium channel, Nav1...
  16. doi Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization
    Hiroshi Watanabe
    Division of Cardiology, Niigata University School of Medicine, Niigata, Japan
    Circ Arrhythm Electrophysiol 4:874-81. 2011
    ..Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical and genetic characteristics are unclear...
  17. pmc The β1-subunit of Na(v)1.5 cardiac sodium channel is required for a dominant negative effect through α-α interaction
    Aurélie Mercier
    Institut de Physiologie et Biologie Cellulaires, FRE 3511, CNRS Université de Poitiers, Pole Biologie Sante, Poitiers, France
    PLoS ONE 7:e48690. 2012
    ....
  18. ncbi Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes
    Ping Yang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn 37232, USA
    Circulation 105:1943-8. 2002
    ..We have previously identified functionally important DNA variants in genes encoding K+ channel ancillary subunits in 11% of an aLQTS cohort...
  19. pmc Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias
    Barry London
    Cardiovascular Institute, University of Pittsburgh Medical Center, Scaife S 572, 200 Lothrop St, Pittsburgh, PA 15213 2582, USA
    Circulation 116:2260-8. 2007
    ..Mutations in the cardiac Na+ channel SCN5A on chromosome 3p21 cause approximately 20% of the cases of Brugada syndrome; most mutations decrease inward Na+ ..
  20. doi Tubulin polymerization modifies cardiac sodium channel expression and gating
    Simona Casini
    Department of Clinical and Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    Cardiovasc Res 85:691-700. 2010
    ..5) function. Therefore, we investigated whether enhanced tubulin polymerization by TXL affects Na(v)1.5 function and expression and whether these effects are beta1-subunit-mediated...
  21. doi Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae
    L Brisson
    INSERM U921, Nutrition, Croissance et Cancer, Universite Francois Rabelais, Faculte de Medecine, Tours, France
    Oncogene 30:2070-6. 2011
    ..Our study suggests that Na(V)1.5 and NHE1 are functionally coupled and enhance the invasiveness of cancer cells by increasing H(+) efflux...
  22. pmc Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems
    Molly Johannessen
    Dept of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
    Am J Physiol Cell Physiol 296:C1049-57. 2009
    ..The modulation of Na(v)1.5 channels by sigma-receptors in the heart suggests an important pathway by which drugs can alter cardiac excitability and rhythmicity...
  23. pmc Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome
    Junhong Gui
    Cardiovascular and Genetic Medicine Research Groups, School of Biomedicine, University of Manchester, Manchester, United Kingdom
    PLoS ONE 5:e10985. 2010
    To identify molecular mechanisms underlying SCN5A-related sick sinus syndrome (SSS), a rare type of SSS, in parallel experiments we elucidated the electrophysiological properties and the cell surface localization of thirteen human Na(v)1...
  24. pmc Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation
    Dawood Darbar
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
    Circulation 117:1927-35. 2008
    ..Here, we tested the hypothesis that vulnerability to AF is associated with variation in SCN5A, the gene encoding the cardiac sodium channel.
  25. ncbi Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease
    Eric Schulze-Bahr
    Department of Cardiology and Angiology, Hospital of the University of Münster, Germany
    Hum Mutat 21:651-2. 2003
    ..Mutations in the cardiac sodium channel gene SCN5A are only known to cause BS...
  26. ncbi Genetic basis and molecular mechanism for idiopathic ventricular fibrillation
    Q Chen
    Department of Pediatrics Cardiology, Baylor College of Medicine, Houston, Texas 77030, USA
    Nature 392:293-6. 1998
    ..malfunction of ion channels could cause the disorder by studying mutations in the cardiac sodium channel gene SCN5A. We have now identified a missense mutation, a splice-donor mutation, and a frameshift mutation in the coding ..
  27. ncbi Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block
    Dao W Wang
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn, and Department of Pediatrics, Medical University of South Carolina, Charleston, USA
    Circulation 105:341-6. 2002
    ..have been associated with heterozygous mutations in the cardiac voltage-gated sodium channel alpha-subunit gene (SCN5A)...
  28. ncbi Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel
    J Wei
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
    Circulation 99:3165-71. 1999
    ..One form, LQT3, is caused by mutations in the cardiac voltage-dependent sodium channel gene, SCN5A. Only 5 SCN5A mutations have been associated with LQTS, and more work is needed to improve correlations between ..
  29. pmc Solution NMR structure of the C-terminal EF-hand domain of human cardiac sodium channel NaV1.5
    Benjamin Chagot
    Department of Anesthesiology, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232 8725, USA
    J Biol Chem 284:6436-45. 2009
    ..These results suggest a molecular basis for the coupling of the intrinsic (EF-hand domain) and extrinsic (calmodulin) components of the calcium-sensing apparatus of NaV1.5...
  30. pmc An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing
    Jamie D Kapplinger
    Department of Medicine, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota, USA
    Heart Rhythm 7:33-46. 2010
    Brugada syndrome (BrS) is a common heritable channelopathy. Mutations in the SCN5A-encoded sodium channel (BrS1) culminate in the most common genotype.
  31. doi Genetic modulation of brugada syndrome by a common polymorphism
    Eric Lizotte
    Montreal Heart Institute and University of Montreal, Montreal, Canada
    J Cardiovasc Electrophysiol 20:1137-41. 2009
    Brugada syndrome predisposes some subjects to ventricular tachyarrhythmias and sudden cardiac death. Mutations in SCN5A gene have been associated with approximately 25% of Brugada syndrome patients...
  32. ncbi Combination of cardiac conduction disease and long QT syndrome caused by mutation T1620K in the cardiac sodium channel
    Ralf Surber
    Department of Internal Medicine I, Friedrich Schiller University Jena, Jena, Germany
    Cardiovasc Res 77:740-8. 2008
    ..mechanism underlying the concomitant occurrence of cardiac conduction disease and long QT syndrome (LQT3), two SCN5A channelopathies that are explained by loss-of-function and gain-of-function, respectively, in the cardiac Na+ ..
  33. ncbi Cardiac sodium channel Na(v)1.5 interacts with and is regulated by the protein tyrosine phosphatase PTPH1
    Thomas Jespersen
    Department of Pharmacology and Toxicology, University of Lausanne, Switzerland
    Biochem Biophys Res Commun 348:1455-62. 2006
    ..The results of this study suggest that tyrosine phosphorylation destabilizes the inactivated state of Na(v)1.5...
  34. ncbi Nucleotide changes in the translated region of SCN5A from Japanese patients with Brugada syndrome and control subjects
    Takenori Takahata
    Department of Clinical Pharmacology, Hirosaki University School of Medicine, 5 Zaifu cho Hirosaki, 036 8562, Aomori, Japan
    Life Sci 72:2391-9. 2003
    The mutations of the SCN5A gene have been implicated to play a pathogenetic role in Brugada syndrome, which causes ventricular fibrillation...
  35. ncbi A novel LQT-3 mutation disrupts an inactivation gate complex with distinct rate-dependent phenotypic consequences
    John R Bankston
    Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Channels (Austin) 1:273-80. 2007
    Inherited mutations of SCN5A, the gene that encodes Na(V)1.5, the alpha subunit of the principle voltage-gated Na(+) channel in the heart, cause congenital Long QT Syndrome variant 3 (LQT-3) by perturbation of channel inactivation...
  36. doi Brugada syndrome and abnormal splicing of SCN5A in myotonic dystrophy type 1
    Karim Wahbi
    Service de cardiologie, Universite Paris Descartes, Hopital Cochin, AP HP, 27, rue du Faubourg Saint Jacques, 75014 Paris, France Institut de Myologie, Universite Pierre et Marie Curie, Hopital Pitie Salpetriere, AP HP, 75013 Paris, France Electronic address
    Arch Cardiovasc Dis 106:635-43. 2013
    ..In patients with myotonic dystrophy type 1 (DM1), the mechanisms underlying sudden cardiac death, which occurs in up to 1/3 of patients, are unclear...
  37. ncbi Calmodulin mediates Ca2+ sensitivity of sodium channels
    James Kim
    Department of Pharmacology, Division of Cardiology, Columbia University, New York, New York 10032, USA
    J Biol Chem 279:45004-12. 2004
    ..Together, these data offer new biochemical evidence for Ca2+/CaM modulation of Na+ channel function...
  38. pmc Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations
    Chia Hsiang Hsueh
    Institute of Pharmacology, School of Medicine, National Taiwan University, Taipei, Taiwan
    J Biomed Sci 16:23. 2009
    ..The molecular and cellular mechanisms that lead to Brugada syndrome are not yet completely understood. However, SCN5A is the most well known responsible gene that causes Brugada syndrome...
  39. ncbi Partial expression defect for the SCN5A missense mutation G1406R depends on splice variant background Q1077 and rescue by mexiletine
    Bi Hua Tan
    Dept of Medicine, Univ of Wisconsin, 600 Highland Ave H6 349, Madison, WI 53792, USA
    Am J Physiol Heart Circ Physiol 291:H1822-8. 2006
    Mutations in the cardiac Na(+) channel gene SCN5A cause loss of function and underlie arrhythmia syndromes. SCN5A in humans has two splice variants, one lacking a glutamine at position 1077 (Q1077del) and one containing Q1077...
  40. ncbi Clinical and electrophysiological characteristics of Brugada syndrome caused by a missense mutation in the S5-pore site of SCN5A
    Hideki Itoh
    Department of Information Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan
    J Cardiovasc Electrophysiol 16:378-83. 2005
    Brugada syndrome is an inherited cardiac disorder caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha-subunit, and potentially leads to ventricular fibrillation and sudden death...
  41. ncbi Loss of function associated with novel mutations of the SCN5A gene in patients with Brugada syndrome
    Ghayath Baroudi
    Department of Medicine, Laval University, Québec Heart Institute and Research Centre, Laval Hospital, Sainte Foy
    Can J Cardiol 20:425-30. 2004
    ..Mutations in the SCN5A gene encoding the cardiac voltage-gated Na+ channel (hNav1.5) are associated with Brugada syndrome.
  42. doi A Brugada syndrome mutation (p.S216L) and its modulation by p.H558R polymorphism: standard and dynamic characterization
    Stefano Marangoni
    Department of Biotechnology and Biosciences, University of Milano Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
    Cardiovasc Res 91:606-16. 2011
    The Na(+) channel mutation (p.S216L), previously associated with type 3 long-QT syndrome (LQT3) phenotype, and a common polymorphism (p.H558R) were detected in a patient with an intermittent Brugada syndrome (BS) ECG pattern...
  43. ncbi Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias
    P J Schwartz
    Department of Cardiology, Policlinico S Matteo IRCCS and University of Pavia, Pavia, Italy
    Circulation 103:89-95. 2001
    ..Preliminary observations suggested that the conditions ("triggers") associated with cardiac events may in large part be gene specific...
  44. pmc Extracellular proton modulation of the cardiac voltage-gated sodium channel, Nav1.5
    D K Jones
    Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
    Biophys J 101:2147-56. 2011
    ..Portions of these data were previously reported in abstract form...
  45. pmc Genome-wide association study of electrocardiographic conduction measures in an isolated founder population: Kosrae
    J Gustav Smith
    Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Heart Rhythm 6:634-41. 2009
    ..Cardiac conduction, as assessed by electrocardiographic PR interval and QRS duration, is an important electrophysiological trait and a determinant of arrhythmia risk...
  46. doi Several common variants modulate heart rate, PR interval and QRS duration
    Hilma Holm
    deCODE Genetics, Reykjavik, Iceland
    Nat Genet 42:117-22. 2010
    ..00032, respectively), between TBX5 and advanced atrioventricular block (P = 0.0067), and between SCN10A and pacemaker implantation (P = 0.0029). We also replicated previously described associations with the QT interval...
  47. pmc Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants
    Suraj Kapa
    Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
    Circulation 120:1752-60. 2009
    ..We sought to quantify the value of mutation type and gene/protein region in determining the probability of pathogenicity for mutations...
  48. doi Biology of cardiac sodium channel Nav1.5 expression
    Martin B Rook
    Department of Medical Physiology, Division Heart and Lungs, University Medical Center Utrecht, The Netherlands
    Cardiovasc Res 93:12-23. 2012
    ..Mutations in the gene-encoding Na(v)1.5, SCN5A, have been associated with a variety of arrhythmic disorders, including long QT, Brugada, and sick sinus syndromes ..
  49. pmc Common variants at ten loci influence QT interval duration in the QTGEN Study
    Christopher Newton-Cheh
    Center for Human Genetic Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
    Nat Genet 41:399-406. 2009
    ..We observed associations at P < 5 x 10(-8) with variants in NOS1AP, KCNQ1, KCNE1, KCNH2 and SCN5A, known to be involved in myocardial repolarization and mendelian long-QT syndromes...
  50. ncbi Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis
    Scott P Fraser
    Neuroscience Solutions to Cancer Research Group, Department of Biological Sciences, Imperial College London, UK
    Clin Cancer Res 11:5381-9. 2005
    ..The purpose of this study was to investigate voltage-gated Na(+) channel (VGSC) expression and its possible role in human breast cancer...
  51. pmc Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes
    Peter J Mohler
    Howard Hughes Medical Institute and Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 101:17533-8. 2004
    ..Together with previous work in neurons, these results in cardiomyocytes suggest that ankyrin-G participates in a common pathway for localization of voltage-gated Na(v) channels at sites of function in multiple excitable cell types...
  52. pmc Calcium-dependent regulation of the voltage-gated sodium channel hH1: intrinsic and extrinsic sensors use a common molecular switch
    Vikas N Shah
    Department of Anesthesiology, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 103:3592-7. 2006
    The function of the human cardiac voltage-gated sodium channel Na(V)1.5 (hH1) is regulated in part by binding of calcium to an EF hand in the C-terminal cytoplasmic domain...
  53. pmc Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)
    D Woodrow Benson
    Department of Pediatrics, Cincinnati Children s Hospital, Ohio, USA
    J Clin Invest 112:1019-28. 2003
    ..with disorders of cardiac rhythm and conduction, we screened the alpha subunit of the cardiac sodium channel (SCN5A) as a candidate gene in ten pediatric patients from seven families who were diagnosed with congenital SSS during ..
  54. ncbi Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5A
    Shao Wu Ou
    Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8 35 1 Sakuragaoka, Kagoshima 890 8544, Japan
    Eur J Neurosci 22:793-801. 2005
    ..Sequence analysis has indicated that hNbR1 is highly homologous with human cardiac Nav1.5/SCN5A with > 99% amino acid identity...
  55. ncbi Cardiac sodium channel mutation in atrial fibrillation
    Patrick T Ellinor
    Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Heart Rhythm 5:99-105. 2008
    Mutations in the sodium channel SCN5A have been implicated in many cardiac disorders, including the long QT syndrome, Brugada syndrome, conduction system disease, and dilated cardiomyopathy with atrial arrhythmias.
  56. ncbi A mutation in the human cardiac sodium channel (E161K) contributes to sick sinus syndrome, conduction disease and Brugada syndrome in two families
    Jeroen P P Smits
    Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, The Netherlands
    J Mol Cell Cardiol 38:969-81. 2005
    Mutations in the gene encoding the human cardiac sodium channel (SCN5A) have been associated with three distinct cardiac arrhythmia disorders: the long QT syndrome, the Brugada syndrome and cardiac conduction disease...
  57. ncbi Cardiac sodium channel Nav1.5 is regulated by a multiprotein complex composed of syntrophins and dystrophin
    Bruno Gavillet
    Department of Pharmacology and Toxicology, University of Lausanne, Switzerland
    Circ Res 99:407-14. 2006
    ..5. In the absence of dystrophin, decreased sodium current may explain the alterations in cardiac conduction observed in patients with dystrophinopathies...
  58. ncbi SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia
    William P McNair
    University of Colorado Cardiovascular Institute, Denver, Colo, USA
    Circulation 110:2163-7. 2004
    ..region also contains a locus for right ventricular cardiomyopathy (ARVD5) and the cardiac sodium channel gene (SCN5A), mutations that cause isolated progressive cardiac conduction defect (Lenegre syndrome), long-QT syndrome (LQT3), ..
  59. ncbi Congenital atrial standstill associated with coinheritance of a novel SCN5A mutation and connexin 40 polymorphisms
    Naomasa Makita
    Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Heart Rhythm 2:1128-34. 2005
    Congenital atrial standstill has been linked to SCN5A. Incomplete penetrance observed in atrial standstill has been attributed in part to the digenic inheritance of polymorphisms in the atrial-specific gap junction connexin 40 (Cx40) in ..
  60. ncbi Prevalence of long-QT syndrome gene variants in sudden infant death syndrome
    Marianne Arnestad
    Institute of Forensic Medicine, University of Oslo, Oslo, Norway
    Circulation 115:361-7. 2007
    ..Given the importance and potential implications of these observations, we performed a study to more accurately quantify the contribution to SIDS of LQTS gene mutations and rare variants...
  61. ncbi A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill
    W Antoinette Groenewegen
    Department of Medical Physiology, University Medical Center, Utrecht, The Netherlands
    Circ Res 92:14-22. 2003
    ..Candidate gene screening revealed a novel mutation in the cardiac sodium channel gene SCN5A (D1275N) in all three affected living relatives and in five unaffected relatives, and the deceased relative was an ..
  62. doi Molecular and clinical characterization of a novel SCN5A mutation associated with atrioventricular block and dilated cardiomyopathy
    Junbo Ge
    Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
    Circ Arrhythm Electrophysiol 1:83-92. 2008
    Increased susceptibility to dilated cardiomyopathy has been observed in patients carrying mutations in the SCN5A gene, but the underlying mechanism remains unclear...
  63. doi SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome
    Vincent Probst
    INSERM, UMR915, Nantes, France
    Circ Cardiovasc Genet 2:552-7. 2009
    Mutations in SCN5A are identified in approximately 20% to 30% of probands affected by Brugada syndrome (BrS). However, in familial studies, the relationship between SCN5A mutations and BrS remains poorly understood...
  64. pmc Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel
    M E Gellens
    Department of Medicine, University of Pennsylvania, Philadelphia 19104
    Proc Natl Acad Sci U S A 89:554-8. 1992
    ..The cDNA, designated hH1, encodes a 2016-amino acid protein that is homologous to other members of the sodium channel multigene family and ..
  65. pmc A double tyrosine motif in the cardiac sodium channel domain III-IV linker couples calcium-dependent calmodulin binding to inactivation gating
    Maen F Sarhan
    Department of Anesthesiology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 284:33265-74. 2009
    ..The results demonstrate that calcium-dependent calmodulin binding to the sodium channel inactivation gate double tyrosine motif is required for calcium regulation of the cardiac sodium channel...
  66. ncbi A single Na(+) channel mutation causing both long-QT and Brugada syndromes
    C Bezzina
    Departments of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands
    Circ Res 85:1206-13. 1999
    Mutations in SCN5A, the gene encoding the cardiac Na(+) channel, have been identified in 2 distinct diseases associated with sudden death: one form of the long-QT syndrome (LQT(3)) and the Brugada syndrome...
  67. ncbi Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome
    M B Rook
    Department of Medical Physiology, Utrecht University, The Netherlands
    Cardiovasc Res 44:507-17. 1999
    ..This syndrome is associated with a high mortality rate and has been shown to display familial occurrence...
  68. ncbi Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2
    I Splawski
    Department of Human Genetics, Howard Hughes Medical Institute, Division of Cardiology, Salt Lake City, Utah, USA
    Circulation 102:1178-85. 2000
    ..Five genes have been implicated in Romano-Ward syndrome, the autosomal dominant form of LQTS: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2...
  69. pmc Functional Interactions between Distinct Sodium Channel Cytoplasmic Domains through the Action of Calmodulin
    Franck Potet
    Departments of Anesthesiology, Pharmacology, Medicine, Biochemistry, and Chemistry and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 284:8846-54. 2009
    ..These findings have bearing upon Na(+) channel function in genetically altered channels and under pathophysiologic conditions where [Ca(2+)](i) impacts cardiac conduction...
  70. pmc Common variants at ten loci modulate the QT interval duration in the QTSCD Study
    Arne Pfeufer
    Institute of Human Genetics, Helmholtz Center Munich, Germany
    Nat Genet 41:407-14. 2009
    ..Four loci map near the monogenic long-QT syndrome genes KCNQ1, KCNH2, SCN5A and KCNJ2...
  71. pmc Variable Na(v)1.5 protein expression from the wild-type allele correlates with the penetrance of cardiac conduction disease in the Scn5a(+/-) mouse model
    Anne Laure Leoni
    INSERM, UMR915, l institut du thorax, Nantes, France
    PLoS ONE 5:e9298. 2010
    Loss-of-function mutations in SCN5A, the gene encoding Na(v)1.5 Na+ channel, are associated with inherited cardiac conduction defects and Brugada syndrome, which both exhibit variable phenotypic penetrance of conduction defects...
  72. doi Alternative splicing of Nav1.5: an electrophysiological comparison of 'neonatal' and 'adult' isoforms and critical involvement of a lysine residue
    Rustem Onkal
    Division of Cell and Molecular Biology, Neuroscience Solutions to Cancer Research Group, Sir Alexander Fleming Building, South Kensington Campus, Imperial College London, London, UK
    J Cell Physiol 216:716-26. 2008
    ..5 would (1) modify the channel kinetics and (2) prolong the resultant current, allowing greater intracellular Na(+) influx. Developmental and pathophysiological consequences of such differences are discussed...
  73. pmc The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome
    Naomasa Makita
    Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    J Clin Invest 118:2219-29. 2008
    ..3 long QT syndrome (LQT3) with Brugada syndrome (BrS) is observed in some carriers of mutations in the Na channel SCN5A. While this overlap is important for patient management, the clinical features, prevalence, and mechanisms ..
  74. doi R222Q SCN5A mutation is associated with reversible ventricular ectopy and dilated cardiomyopathy
    Stefan A Mann
    Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
    J Am Coll Cardiol 60:1566-73. 2012
    The goal of this study was to characterize a variant in the SCN5A gene that encodes the alpha-subunit of the cardiac sodium channel, Nav1...
  75. ncbi Molecular mechanism for an inherited cardiac arrhythmia
    P B Bennett
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Nature 376:683-5. 1995
    ..has been linked to a mutation in the gene encoding the human heart voltage-gated sodium-channel alpha-subunit (SCN5A on chromosome 3p21)...
  76. doi SAP97 and dystrophin macromolecular complexes determine two pools of cardiac sodium channels Nav1.5 in cardiomyocytes
    Séverine Petitprez
    University of Bern, Department of Clinical Research, Murtenstrasse, 35, 3010 Bern, Switzerland
    Circ Res 108:294-304. 2011
    ..As dystrophin is absent at the intercalated discs, Na(v)1.5 could potentially interact with other, yet unknown, proteins at this site...
  77. ncbi Expression and intracellular localization of an SCN5A double mutant R1232W/T1620M implicated in Brugada syndrome
    Ghayath Baroudi
    Department of Medicine, Laval University and Quebec Heart Institute, Laval Hospital Research Center, Sainte Foy, Quebec, Canada
    Circ Res 90:E11-6. 2002
    Brugada syndrome is an inherited cardiac disorder caused by mutations in the cardiac sodium channel gene, SCN5A, that leads to ventricular fibrillation and sudden death...
  78. ncbi Novel LQT-3 mutation affects Na+ channel activity through interactions between alpha- and beta1-subunits
    R H An
    Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Circ Res 83:141-6. 1998
    ..Previously studied LQT-3 mutations of SCN5A (or hH1), the gene that encodes the human Na+ channel alpha-subunit, have been shown to encode voltage-gated Na+ ..
  79. doi Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies
    Paola G Meregalli
    Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
    Heart Rhythm 6:341-8. 2009
    Patients carrying loss-of-function SCN5A mutations linked to Brugada syndrome (BrS) or progressive cardiac conduction disease (PCCD) are at risk of sudden cardiac death at a young age...
  80. pmc Sodium channel mutations and susceptibility to heart failure and atrial fibrillation
    Timothy M Olson
    Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA
    JAMA 293:447-54. 2005
    ..Recently, genetic defects in calcium and potassium regulation have been discovered in patients with DCM, implicating an alternative disease mechanism. The full spectrum of genetic defects in DCM, however, has not been established...
  81. ncbi A ubiquitous splice variant and a common polymorphism affect heterologous expression of recombinant human SCN5A heart sodium channels
    Jonathan C Makielski
    Department of Medicine, University of Wisconsin, 600 Highland Ave H6 349, Madison, Wis 53792, USA
    Circ Res 93:821-8. 2003
    Amino acid sequence variations in SCN5A are known to affect function of wild-type channels and also those with coexisting mutations; therefore, it is important to know the exact sequence and function of channels most commonly present in ..
  82. doi Mutation-specific effects of polymorphism H558R in SCN5A-related sick sinus syndrome
    Junhong Gui
    Cardiovascular Research Group, School of Clinical and Laboratory Sciences, University of Manchester, Manchester, UK
    J Cardiovasc Electrophysiol 21:564-73. 2010
    Mutations in SCN5A, the gene encoding alpha subunit of cardiac type sodium channel, Na(v)1.5, lead to familial sick sinus syndrome (SSS)...
  83. pmc Correlations between clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in the cardiac Na+ channel
    Y Zhang
    Cardiovascular Ion Channel Disease Laboratory, Department of Paediatrics, First Affiliated Hospital, Medical College of Xi an Jiaotong University, Xi an, China
    Acta Physiol (Oxf) 194:311-23. 2008
    ..We compared the clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in domain II (S5-S6) of human, hNa(v)1.5, cardiac Na(+) channels...
  84. ncbi Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome
    Andrea Frustaci
    Heart and Great Vessels Department, Attilio Reale, La Sapienza University, Rome, Italy
    Circulation 112:3680-7. 2005
    ..The role of structural heart disease and sodium channel dysfunction in the induction of electrical instability in Brugada syndrome is still debated...
  85. ncbi High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations
    Takeru Makiyama
    Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
    J Am Coll Cardiol 46:2100-6. 2005
    We carried out a complete screening of the SCN5A gene in 38 Japanese patients with Brugada syndrome to investigate the genotype-phenotype relationship.
  86. ncbi Common sodium channel promoter haplotype in asian subjects underlies variability in cardiac conduction
    Connie R Bezzina
    Experimental and Molecular Cardiology Group, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Circulation 113:338-44. 2006
    ..Loss of function mutations in SCN5A, encoding the cardiac sodium channel, are one cause of the Brugada syndrome, associated with slow conduction and a ..
  87. pmc A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y
    Leigh D Plant
    Department of Pediatrics and Institute for Molecular Pediatric Sciences, Pritzker School of Medicine, Biological Sciences Division, University of Chicago, Chicago, Illinois 60637, USA
    J Clin Invest 116:430-5. 2006
    ..While 2 cases have been associated with mutations in type Valpha, cardiac voltage-gated sodium channels (SCN5A), the "Back to Sleep" campaign has decreased SIDS prevalence, consistent with a role for environmental influences ..
  88. pmc Overrepresentation of the proarrhythmic, sudden death predisposing sodium channel polymorphism S1103Y in a population-based cohort of African-American sudden infant death syndrome
    David W Van Norstrand
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA
    Heart Rhythm 5:712-5. 2008
    The S1103Y-SCN5A polymorphism has been implicated as a proarrhythmic, sudden death predisposing risk factor in African Americans, including one postmortem investigation of African-American infants with sudden infant death syndrome (SIDS).
  89. pmc Subepicardial phase 0 block and discontinuous transmural conduction underlie right precordial ST-segment elevation by a SCN5A loss-of-function mutation
    Marketa Bebarova
    Dept of Cardiology, Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht, 6202 AZ, Maastricht, The Netherlands
    Am J Physiol Heart Circ Physiol 295:H48-58. 2008
    ..with a Na(+) current (I(Na)) loss-of-function mutation from studies in a Dutch kindred with the COOH-terminal SCN5A variant p.Phe2004Leu...
  90. ncbi Characterization of a novel SCN5A mutation associated with Brugada syndrome reveals involvement of DIIIS4-S5 linker in slow inactivation
    Simona Casini
    Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Cardiovasc Res 76:418-29. 2007
    Mutations in SCN5A, the gene encoding the alpha-subunit of the cardiac sodium channel (Na(v)1.5), have been associated with various inherited arrhythmia syndromes, including Brugada syndrome (BrS)...
  91. ncbi Cardiac sodium channel dysfunction in sudden infant death syndrome
    Dao W Wang
    Departments of Pharmacology, Vanderbilt University, Nashville, Tenn, USA
    Circulation 115:368-76. 2007
    Mutations in genes responsible for the congenital long-QT syndrome, especially SCN5A, have been identified in some cases of sudden infant death syndrome...
  92. doi Cardiac ion channel gene mutations in sudden infant death syndrome
    Tesshu Otagiri
    Department of Pediatrics, Yamagata University School of Medicine, Yamagata 990 9585, Japan
    Pediatr Res 64:482-7. 2008
    ..genes causing long QT syndrome in 42 Japanese SIDS victims and found five mutations, KCNQ1-K598R, KCNH2-T895M, SCN5A-F532C, SCN5A-G1084S, and SCN5A-F1705S, in four cases; one case had both KCNH2-T895M and SCN5A-G1084S...
  93. pmc Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada syndrome
    Jonathan M Cordeiro
    Department of Experimental Cardiology, Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501, USA
    Circulation 114:2026-33. 2006
    Loss-of-function mutations in SCN5A have been associated with the Brugada syndrome. We report the first Brugada syndrome family with compound heterozygous mutations in SCN5A...
  94. doi Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome
    Séverine Petitprez
    Department of Pharmacology and Toxicology, University of Lausanne, 27, Bugnon, 1005 Lausanne, Vaud, Switzerland
    Cardiovasc Res 78:494-504. 2008
    ..BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Na(v)1.5...
  95. ncbi Modulation of Nav1.5 channel function by an alternatively spliced sequence in the DII/DIII linker region
    Juan A Camacho
    Institute of Physiology II, Friedrich Schiller University, 07740 Jena, Germany
    J Biol Chem 281:9498-506. 2006
    ..Moreover, the present study identified novel short sequence motifs within this amphiphilic region that specifically affect the voltage dependence of steady-state activation and inactivation and current amplitude of human Na(v)1.5...
  96. ncbi A novel mutation in the SCN5A gene is associated with Brugada syndrome
    Dong Jik Shin
    Cardiovascular Genome Center, Yonsei University Medical Center, Seoul, Republic of Korea
    Life Sci 80:716-24. 2007
    ..inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha-subunit (Na(v)1.5)...
  97. ncbi Role of SCN5A Y1102 polymorphism in sudden cardiac death in blacks
    Allen Burke
    Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC, USA
    Circulation 112:798-802. 2005
    The Y1102 polymorphism of the cardiac sodium channel (SCN5A) gene has been found in 13% of black Americans. It has been linked to lethal arrhythmias in black families with ventricular tachycardia...
  98. ncbi Cardiac conduction defects associate with mutations in SCN5A
    J J Schott
    Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Moléculaires, INSERM CJF96 01, France
    Nat Genet 23:20-1. 1999
  99. ncbi Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes
    I Rivolta
    Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    J Biol Chem 276:30623-30. 2001
    Defects of the SCN5A gene encoding the cardiac sodium channel alpha-subunit are associated with both the long QT-3 (LQT-3) subtype of long-QT syndrome and Brugada syndrome (BrS)...
  100. ncbi Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients
    Jeroen P P Smits
    Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands
    J Am Coll Cardiol 40:350-6. 2002
    ..relationship exists in Brugada syndrome (BS) by trying to distinguish BS patients with (carriers) and those without (non-carriers) a mutation in the gene encoding the cardiac sodium channel (SCN5A) using clinical parameters.
  101. ncbi A novel mutation in SCN5A, delQKP 1507-1509, causing long QT syndrome: role of Q1507 residue in sodium channel inactivation
    Dagmar I Keller
    INSERM U582, IFR No 14, Pitie Salpetriere Hospital, Paris, France
    J Mol Cell Cardiol 35:1513-21. 2003
    Inherited long QT syndrome (LQTS) is caused by mutations in six genes including SCN5A, encoding the alpha-subunit of the human cardiac voltage-dependent sodium channel hNa(v)1.5...

Research Grants72

  1. COOPERATIVE MULTICENTER REPRODUCTIVE MEDICINE NETWORK
    Christos Coutifaris; Fiscal Year: 2013
    ..The third, the first IVF clinical trial performed by the RMN, evaluating the effect of physiologic (5%) oxygen tension on delivery rates, ..
  2. Non-invasive method to evaluate the quality of human oocytes and embryos
    XINGQI JOHN ZHANG; Fiscal Year: 2013
    ..This technology, if success, will for the first time, provide a quantitative measurement of the in vitro fertilized IVF) embryos. It will help users to non-invasively identify the best embryo for transfer...
  3. The Utility of Empiric Medical Treatment of Infertile Oligo-asthenospermic Men
    Peter R Casson; Fiscal Year: 2013
    ..In Vitro Fertilization with intracytoplasmic sperm injection (IVF/ICSI), while effective, is expensive, emotionally traumatizing, and may carry significant potential risks...
  4. Comprehensive aneuploidy diagnosis in single cells
    Nury Steuerwald; Fiscal Year: 2005
    ..cavity, or by laser capture microdissection; 3) preimplantation genetic diagnosis (PGD) and in vitro fertilization (IVF), the area addressed in detail in this proposal...
  5. CONVENTIONAL INFERTILITY THERAPY VS FAST TRACK TO IVF
    Richard Reindollar; Fiscal Year: 2004
    This study is designed to determine the cost-effectiveness of a fast track to in vitro fertilization (IVF) infertility therapy by conducting a randomized prospective clinical trial to compare its success rates and costs to that of ..
  6. Cooperative Multicenter Reproductive Medicine Network (U10)
    MARCELLE IVONNE CEDARS; Fiscal Year: 2013
    ..time to delivery after ovarian stimulation and intrauterine insemination followed by in vitro fertilization (IVF)/intracytoplasmiG sperm injection (ICSI);2) Determine if coQIO supplementation affects oocyte developmental ..
  7. Improvement in Oocyte In Vitro Maturation (IVM) Using Microfluidic Culture
    ARTHUR GERSHOWITZ; Fiscal Year: 2010
    ..medication side effects, and health risks to patients compared with traditional in vitro fertilization (IVF)...
  8. Adverse Outcomes of Assisted Reproductive Technologies: Genetics or Epigenetics?
    Margareta Pisarska; Fiscal Year: 2013
    ..As a result, the use of assisted reproductive technologies (ART), including in vitro fertilization (IVF) has risen dramatically, so that nearly 1% of babies born in the US are conceived using IVF...
  9. Improved Implantation and Pregnancy Using Microfluidic Embryo Culture
    Xiaoyue Zhu; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Significant progress has been made in Vitro Fertilization (IVF) since the fist test tube baby was born in 1978. IVF pregnancy success rates in the U.S...
  10. HBEGF - A Role In Human Implantation
    Richard Leach; Fiscal Year: 2005
    ..cycle and implantation, nor is it known how the hormonal manipulations used during in vitro fertilization (IVF) alter their expression patterns...
  11. STEM CELL DERIVATION OF TWO NEOTROPICAL PRIMATE SPECIES
    A Michele Schuler; Fiscal Year: 2010
    ..To determine the optimal method for intra-cytoplasmic sperm injection (ICSI) and/or in vitro fertilization (IVF) in squirrel and owl monkeys including optimal culture techniques for oocytes and embryos;(3) To optimize ..
  12. Maternal Pesticide Exposure and Pregnancy Outcomes
    Russ Hauser; Fiscal Year: 2009
    ..we will explore the developmental toxicity of chlorinated compounds in women undergoing in vitro fertilization (IVF), which can be used as a model to assess early development, normally unobservable...
  13. Analysis of epigenetic regulation in early mammalian embryos via RNA interference
    Charles R Long; Fiscal Year: 2010
    ..re-established during early embryonic development, concomitant with the period of embryo culture following IVF in fertility clinics...
  14. Stability of epigenetic structures in ART children
    Carmen Sapienza; Fiscal Year: 2010
    ..In fact, more than a million children have been born as the result of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and children conceived by these procedures account for more than 1% of ..
  15. Noninvasive assessment of embryo implantation potential using 1H NMR metabonomics
    Paolo Rinaudo; Fiscal Year: 2010
    ..In vitro fertilization (IVF) treatment has significantly increased the number of multiple births by the transfer multiple embryos in a single ..
  16. The Role of Acid-active Hyaluronidases in Sperm Function
    PATRICIA ANASTASIA DELEON; Fiscal Year: 2010
    ..Critical levels of hyases are required for the success of in vitro fertilization (IVF) where recombinant SPAM1 has been used...
  17. Long-term Follow-Up of Infertility Patients: A Pilot Study
    Francine Grodstein; Fiscal Year: 2010
    ..In 2002, approximately 1% of all babies born in the US were a result of in- vitro fertilization (IVF)...
  18. Institute for Biogenesis Research: COBRE
    WILLIAM S WARD; Fiscal Year: 2012
    ..the development of intracytoplasmic sperm injection (ICSI), the principles underlying in vitro fertilization (IVF) in mammals, the first demonstration of repetitive mammalian cloning, and ICSI-mediated transgenic mice...
  19. IBR COBRE ADMINISTRATIVE CORE
    WILLIAM S WARD; Fiscal Year: 2011
    ..the development of intracytoplasmic sperm injection (ICSI), the principles underlying in vitro fertilization (IVF) in mammals, the first demonstration of repetitive mammalian cloning, and ICSI-mediated transgenic mice...
  20. Course and predictors of depressive relapse during IVF
    Marlene P Freeman; Fiscal Year: 2013
    ..guidelines on which to rely in order to advise women with histories of MDD who plan in vitro fertilization (IVF) or other assisted reproductive procedures...
  21. Maternal Phthalate Exposure and Infertility, Fetal Loss
    Russ Hauser; Fiscal Year: 2007
    ..In the NIEHS study, infertile couples referred to the Massachusetts General Hospital for in vitro fertilization (IVF) are recruited. From both the male and female partner, we collect questionnaire data and biological specimens...
  22. REPRODUCTIVE MEDICINE AND THE LAW WORKSHOPS
    Robert Rebar; Fiscal Year: 2007
    ..substantially as refinements in assisted reproductive technologies (ART), including in vitro fertilization (IVF), have extended family-building potential to patients who previously had little hope of conception...
  23. Paracrine dysregulation of oocyte competence in PCOS
    DANIEL DUMESIC; Fiscal Year: 2006
    ..During gonadotropin stimulation for in vitro fertilization (IVF), PCOS women experience decreased fecundity and increased pregnancy loss...
  24. Trophoblast MHC-I: Trigger for Immune-Mediated Rejection of Cloned Bovine Fetuses
    Kenneth L White; Fiscal Year: 2011
    ..in human and bovine pregnancies established by assisted reproductive technologies such as in vitro fertilization (IVF)...
  25. Microinjection Station for Utah Transgenic and Gene Targeting Mouse Core
    SUSAN JENIFER TAMOWSKI; Fiscal Year: 2010
    ..ICSI (intracytoplasmic sperm injection) is used to directly inject immobile sperm into an egg. This procedure is used if normal IVF or AIVF is unsuccessful. It is imperative that the injector have excellent optics in this procedure.
  26. Families created by assisted reproduction: parenting and child development
    SUSAN ESTHER GOLOMBOK; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Since the birth of the first baby through in vitro fertilization (IVF) in 1978, more than 1 million babies have been born as a result of assisted reproduction...
  27. Function of RUNX transcription factors in COCs
    Misung Jo; Fiscal Year: 2013
    ..target genes to oocyte quality, fertilization, and embryo development using COCs obtained from women undergoing IVF (Aim #4). These human studies will serve as a foundation for future translational/clinical application...
  28. Novel Informatics for Highly Reliable Multi-Locus Allele Calling for Embryo Scree
    Matthew Rabinowitz; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): In 2006, across the globe, more than 800,000 in-vitro fertilization (IVF) cycles were run. Of 150,000 cycles run in the US, roughly 10,000 involved pre-implantation genetic diagnosis (PGD)...
  29. SPERM PROGESTERONE RECEPTOR, K+ CHANNEL & PB EXPOSURE
    Asha Jacob; Fiscal Year: 1999
    ..Adapted from the Investigator's Abstract) In a blinded study of couples undergoing in vitro fertilization, (IVF) more than 40% of the males had serum levels of lead above the action limit for occupationally exposed workers...
  30. Transgenesis-Ready Mice with Tn5 Transposase
    JOANNE EBESU; Fiscal Year: 2007
    ..designed to intercept the sperm chromatin during its decondensation stage soon after in-vitro fertilization (IVF)...
  31. EFFICACY OF MOUSE SPERM CRYOPRESERVATION
    LARRY MOBRAATEN; Fiscal Year: 2001
    ..2) Enhance in vitro fertilization (IVF) for gametes from different inbred strains...
  32. Optimal Infertility Therapy RCT: Women 40 and Older
    Richard Reindollar; Fiscal Year: 2007
    ..couples will be randomized to one of three treatment arms: four cycles of immediate in vitro fertilization (IVF), two cycles of clomiphene/intrauterine insemination (IUI) followed by four cycles of IVF, or two cycles of FSH/IUI ..
  33. MORPHOLOGY-BASED RATING OF EGG DEVELOPMENT POTENTIAL
    Clifford Hoyt; Fiscal Year: 2000
    Since the first in vitro fertilization baby in 1978, IVF has brought significant benefit to tens of thousands of otherwise infertile couples...
  34. NUCLEAR TRANSFER IN RHESUS MONKEYS
    Don Wolf; Fiscal Year: 2001
    ..The PI has established a successful in vitro fertilization (IVF) program at the ORPRC where rhesus monkeys have been produced for the first time by nuclear transfer from embryonic ..
  35. Validation of Novel Infertility Biomarker
    PETER SUTOVSKY SUTOVSKY; Fiscal Year: 2012
    ..SPTRX3 based test will allow clinicians to make a treatment decision between intrauterine insemination (IUI) versus IVF/ICSI in the general infertility clinic-population...
  36. Midcareer Investigator Award in Patient Oriented Research
    Kurt T Barnhart; Fiscal Year: 2013
    ..Aim #2 is use a three arm cohort study assessing childhood development in children conceived with IVF, superovulation or without medical assistance...
  37. GLUTS AND GLUCOSE TRANSPORT IN THE MOUSE BLASTOCYST
    Kelle H Moley; Fiscal Year: 2012
    ..to improve pregnancy rates in patients with diabetes, recurrent pregnancy loss as well as patients undergoing IVF. PUBLIC HEALTH RELEVANCE: In this proposal, we hypothesize that basal autophagy in the murine blastocyst is ..
  38. UNDERSTANDING OVARIAN CONTROL IN RARE BIOMEDICAL MODELS
    KATHARINE PELICAN; Fiscal Year: 2006
    ..ovarian inhibition, and to apply these protocols to improve ovarian response to gonadotropin stimulation for AI and IVF. This, in turn, will help propagate cats valuable to biomedical research and conserve endangered felid species...
  39. Luteal Progesterone Supplementation in Clomiphene Citrate-IUI Cycles
    KARL RICHARD HANSEN; Fiscal Year: 2013
    ..Given the low cost and high utilization of these treatments as compared to the cost of IVF, even small improvements in live-birth rates would be clinically meaningful...
  40. Use of OET to assess mouse preimplantation quality for uterine transfer
    MAURICE MARCEL GARCIA; Fiscal Year: 2013
    ..Our current limited ability to predict in vitro embryo quality is a well-recognized source of limited IVF success and adverse outcomes. Dr...
  41. Derivation of Mature Oocytes from Human Primordial Follicles
    AARON JW HSUEH; Fiscal Year: 2010
    ..Mature oocytes could be retrieved from these ovaries for IVF and blastocyst formation...
  42. Minimum Y gene complement necessary for successful ART
    MONIKA WARD; Fiscal Year: 2009
    ..We also show that assisted reproduction by ICSI and IVF enable the generation of live offspring from subfertile and infertile males with Y chromosome deficiencies...
  43. Mechanisms of Reduced Fecundity in Endometriosis: A role for MMPs and TIMPs
    KATHY L TIMMS; Fiscal Year: 2012
    ..Such approaches are paramount to shift from surgical or chemical obliteration of lesions or repeated attempts at IVF. Using an endometriosis model which emulates human disease and comparing the data to that from women will ..
  44. AMP-activated protein kinase management will improve oocyte cryopreservation
    Daniel Allen Rappolee; Fiscal Year: 2010
    ..doses of AMPK agonist or antagonist during prefreeze handling, freeze down medium, and during culture after thaw, IVF and culture to blastocyst stage...
  45. Development of an Economic Process to Store and Recover Homozygous Mouse Strains
    MICHAEL VAN WILES; Fiscal Year: 2010
    ..A major limitation to human IVF is the paucity of oocytes...
  46. Molecular mechanisms of hERG1 channel activators
    MICHAEL CRAIG SANGUINETTI; Fiscal Year: 2013
    ..Mechanism-based pharmacotherapy (e.g., mexilitine for LQT3) has been explored in the past, but little is known about the mechanisms of action or therapeutic utility of the ..
  47. Molecular Markers of Oocyte Quality and Competence
    Graham Jenkin; Fiscal Year: 2007
    ..growth and development, oocyte, embryonic stem cell and embryo manipulation; including programming, reprogramming, IVF and embryo manipulation and culture and cryopreservation, placentation and the study of the Barker Hypothesis (the ..
  48. A Primate In Vitro Implantation Model
    Thaddeus Golos; Fiscal Year: 2009
    ..We thus propose to adapt this paradigm and expand it to an in vitro implantation model with IVF-produced rhesus monkey embryos with 2 specific aims: Specific Aim 1...
  49. Penn Center for Study of Epigenetics in Reproduction
    Marisa S Bartolomei; Fiscal Year: 2013
    ..and gene expression in newborns, extra-embryonic tissues and on trophoblast differentiation and function following IVF pregnancies and pregnancies resulting from unassisted conception...
  50. Epididymal PMCA4 Expression Functional Impact and Mechanism of Sperm Uptake
    PATRICIA ANASTASIA DELEON; Fiscal Year: 2013
    ..of PMCA4a and other TM proteins, and to determine the possibility of using artificial vesicles in ART (assisted reproductive technology) to deliver the proteins to deficient sperm to improve their fertilizing capabilities, via IVF.
  51. Supporting Human ART Through Basic Science
    Barry Bavister; Fiscal Year: 2004
    ..clinical embryologists and medical directors) in the latest basic and applied science relevant to their IVF programs, and (2) foster communication, exchange of information and awareness of how animal embryo research can ..
  52. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    ALFRED GEORGE; Fiscal Year: 2009
    ..We have recently shifted our focus from studies of the two striated muscle sodium channel genes (SCN4A, SCN5A) to investigations of brain sodium channel genes and their role in inherited epilepsies...
  53. THERAPUTIC TRIAL IN PATIENTS WITH LQTS 3 GENE MUTATION
    Arthur Moss; Fiscal Year: 2002
    ..Recently, four genetic forms of LQTS have been identified including LQT3, a sodium-channel gene mutation (SCN5A, deltaKPQ deletion) with impairment of sodium-channel inactivation...
  54. A NOVEL PH DEPENDENT POTASSIUM CHANNEL IN MAMMALIAN SPERM
    Celia Santi; Fiscal Year: 2009
    ..2. Studies of SLO3 channels may contribute to in vitro fertilization (IVF) techniques...
  55. Role of spectrin/ankyrin-G complex in myocyte signaling and cardiac excitability
    Peter J Mohler; Fiscal Year: 2013
    ..abstract_text> ..
  56. Human Macrophage Sodium Channels: Novel Targets for Inflammatory Diseases
    Michael D Carrithers; Fiscal Year: 2013
    ..The research proposed examines unique features of human macrophages at the cellular level. Such studies are needed to develop effective anti-macrophage treatments for three serious human diseases -- HIV, TB, and MS. ..
  57. Molecular Dissection of Calmodulin Domain Functions
    Madeline A Shea; Fiscal Year: 2013
    ....
  58. MECHANOTRANSDUCTION IN INTESTINAL SMOOTH MUSCLE CELLS
    Gianrico Farrugia; Fiscal Year: 2013
    ..5, the a subunit of which is encoded by SCN5A and that Nav1.5 is mechanosensitive. Mechano-regulation of Nav1...
  59. Molecular Mechanisms of Cardiac Arrhythmias
    Qing Wang; Fiscal Year: 2005
    ..In the proposed studies we plan to develop and characterize LQT- and IVF-animal models in which SCN5A (the cardiac sodium channel gene) mutations are engineered into the mouse genome to further explore the etiology ..
  60. Sodium Channels and Cardiac Arrhythmias
    Isabelle Deschenes; Fiscal Year: 2013
    ..2. Investigate the mechanisms by which SCN5A polymorphisms can modulate the function of mutated sodium channels. 3...
  61. Role of serum- and glucocorticoid-regulated kinase-1 in electrical remodeling
    Anthony Rosenzweig; Fiscal Year: 2013
    ..downstream effects including modulation of ion channels such as potassium channels and the cardiac sodium channel, SCN5a. While we have previously shown that SGK1 regulates cardiomyocyte (CM) survival and growth in vitro, its role in ..
  62. Local anesthetic receptor in peripheral Na+ channels
    GING K WANG; Fiscal Year: 2013
    ..Our goals are to delimit such a receptor in peripheral Nav1.7 and Nav1.8 channels, to resolve the drug/receptor interactions during state transitions, and to explore this receptor site for novel pain therapeutics. ..
  63. Neural Circulatory Control in the Long QT Syndrome
    Virend Somers; Fiscal Year: 2006
    ..by mutations in cardiac ion channel genes, the commonest known mutations being classified as LQT1, LQT2, and LQT3. The degree of QT prolongation is an independent risk factor for cardiac events...
  64. Regulation of the Cardiac Sodium Channel by SIRTUIN1
    Barry London; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The cardiac Na+ channel SCN5A (Nav1...
  65. MULTI-ANALYTE WAVEGUIDE IMMUNOSENSING
    JAMES HERRON; Fiscal Year: 2002
    ..LQTS has been linked to genetic polymorphisms in four genes (KVLQT1,HERG, SCN5A & KCNE1) that encode for cardiac ion channels...
  66. Neonatal Long QT Syndrome and Sudden Infant Death
    Alfred L George; Fiscal Year: 2013
    ..For exampe, mutations in SCN5A encoding the cardiac sodium channel have been associated with a spectrum of increased sudden death risk extending ..
  67. CaMKII-dependent regulation of cardiac excitability
    THOMAS JEFFREY HUND; Fiscal Year: 2013
    ..5 and cell excitability, and identify novel mechanisms for arrhythmias in both congenital and acquired heart disease. ..
  68. Metabolic Regulation of Sodium Channels
    Samuel C Dudley; Fiscal Year: 2013
    ..injury from many causes is associated with altered metabolism and downregulation of the cardiac sodium channel (SCN5A). Recently, data demonstrated that the SCN5A was substantially and immediately modulated by pyridine nucleotides...
  69. Isolating and Characterizing Atypical Arrhythmia Genes
    Mark Keating; Fiscal Year: 2005
    ..Define and characterize common variants in SCN5A that contribute to drug-induced long QT syndrome...
  70. Regions of Na channel involved in permeation and gating
    Nipavan Chiamvimonvat; Fiscal Year: 2002
    ..g., one form of congenital long QT syndrome (LQT3). The long-term goals of this proposal are to understand the molecular basis for the function of Na+ channels...
  71. Positional Cloning and Candidate Gene Approach to Familial Atrial Fibrilation
    Dawood Darbar; Fiscal Year: 2012
    ..There is mounting evidence supporting the role of SCN5A, the gene encoding the human cardiac sodium channel, in AF...
  72. SCOR IN SUDDEN CARDIAC DEATH
    Robert Lux; Fiscal Year: 2004
    ..identify new mutations underlying the hereditary long QT syndrome (LQT) and idiopathic ventricular fibrillation (IVF), both of which are caused by ion channel dysfunction during repolarization...