Genetic variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes

Matthew R G TaylorLuisa Mestroni


Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited genetic myocardial disease characterized by fibrofatty replacement of the myocardium and a predisposition to cardiac arrhythmias and sudden death. We evaluated the cardiomyopathy gene titin (TTN) as a candidate ARVC gene because of its proximity to an ARVC locus at position 2q32 and the connection of the titin protein to the transitional junction at intercalated disks. All 312 titin exons known to be expressed in human cardiac titin and the complete 3' untranslated region were sequenced in 38 ARVC families. Eight unique TTN variants were detected in 7 families, including a prominent Thr2896Ile mutation that showed complete segregation with the ARVC phenotype in 1 large family. The Thr2896IIe mutation maps within a highly conserved immunoglobulin-like fold (Ig10 domain) located in the spring region of titin. Native gel electrophoresis, nuclear magnetic resonance, intrinsic fluorescence, and proteolysis assays of wild-type and mutant Ig10 domains revealed that the Thr2896IIe exchange reduces the structural stability and increases the propensity for degradation of the Ig10 domain. The phenotype of TTN variant carriers was characterized by a history of sudden de...Continue Reading


Nov 9, 2012·Current Heart Failure Reports·Amy Curry Sturm
Jun 4, 2013·Current Treatment Options in Cardiovascular Medicine·Cynthia A James, Hugh Calkins
Aug 21, 2013·European Journal of Medical Genetics·O CampuzanoR Brugada
Mar 15, 2013·European Journal of Human Genetics : EJHG·Ilena Egle Astrid Li MuraAlessandra Rampazzo
May 9, 2012·Nature Medicine·Wolfgang A Linke, Sandra Bücker
Nov 30, 2011·Nature Reviews. Cardiology·Cristina BassoGaetano Thiene
Jan 9, 2013·The Journal of Biological Chemistry·Brian R AndersonHenk L Granzier
Dec 27, 2011·European Heart Journal·Giovanni QuartaPerry M Elliott
Jul 17, 2013·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Estelle GandjbakhchEric Villard
Jul 6, 2012·Circulation. Cardiovascular Genetics·Jessica R GolbusElizabeth M McNally
Feb 27, 2013·Circulation·Martin M LeWinter, Henk L Granzier
Jan 3, 2013·The Journal of Clinical Investigation·Elizabeth M McNallyMegan J Puckelwartz
Sep 28, 2013·Journal of Cardiovascular Pharmacology·Martin M LeWinter, Henk L Granzier
Aug 3, 2013·Biomarkers in Medicine·P Garcia-PaviaL Alonso-Pulpon
Aug 27, 2014·Journal of Medical Genetics·Francesca BrunFamilial Cardiomyopathy Registry
May 13, 2014·Netherlands Heart Journal : Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation·Judith A GroenewegRichard N Hauer
Oct 31, 2015·International Journal of Molecular Sciences·O CampuzanoR Brugada
Apr 24, 2014·Cell Communication & Adhesion·Dipal M Patel, Kathleen J Green
Feb 1, 2013·Revista Española De Cardiología·Àngel MoyaJosep Lluis Mont
May 25, 2012·Revista Española De Cardiología·Giovanni Quarta, Perry M Elliott
Mar 6, 2012·Progress in Cardiovascular Diseases·Jonathan D S SnidermanWilliam J McKenna
Feb 4, 2012·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Ting-Ting HongRobin M Shaw
Mar 17, 2012·European Journal of Medical Genetics·O CampuzanoR Brugada
Feb 7, 2012·Revista Portuguesa De Cardiologia : Orgão Oficial Da Sociedade Portuguesa De Cardiologia = Portuguese Journal of Cardiology : an Official Journal of the Portuguese Society of Cardiology·Perry M Elliott, Saidi A Mohiddin
Apr 30, 2015·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Dongdong QueLei Liu
Sep 6, 2014·Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance·Anneline S J M te RieleDavid A Bluemke
Nov 1, 2015·The Canadian Journal of Cardiology·Brenda Gerull
Jul 5, 2013·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·V Ramesh Iyer, Alvin J Chin
Jan 8, 2014·Annals of Neurology·Anni EviläBjarne Udd
Jul 2, 2014·Human Mutation·Claire ChauveauAna Ferreiro
Apr 4, 2016·Orphanet Journal of Rare Diseases·Kalliopi PilichouCristina Basso
Jul 22, 2014·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Nathalie Roux-BuissonPhilippe Charron
Aug 5, 2014·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Judith A GroenewegDennis Dooijes
Jan 24, 2015·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Jose Maria Lopez-AyalaJuan Ramon Gimeno


Nov 1, 1988·Journal of the American College of Cardiology·Andrea NavaG Fasoli
Nov 15, 1997·Journal of the American College of Cardiology·Domenico CorradoF Camerini
Jul 3, 1999·Journal of Molecular Biology·F Fraternali, A Pastore
Aug 27, 1999·Biochemical and Biophysical Research Communications·M SatohAkinori Kimura
Dec 2, 2000·Nature Structural Biology·H LiJ M Fernandez
Sep 15, 2001·American Journal of Physiology. Heart and Circulatory Physiology·K TrombitásHenk L Granzier
Jan 19, 2002·The Journal of Biological Chemistry·Kaori WatanabeHenk L Granzier
Feb 16, 2002·Biochemical and Biophysical Research Communications·Manatsu Itoh-SatohAkinori Kimura
Mar 5, 2002·Genome Research·Pauline C Ng, Steven Henikoff
Aug 31, 2002·Nucleic Acids Research·Vasily RamenskyShamil Sunyaev
Feb 21, 2004·Circulation Research·Henk L Granzier, Siegfried Labeit
Feb 9, 2006·Journal of Muscle Research and Cell Motility·Yuji MatsumotoAkinori Kimura
Feb 17, 2006·Molecular Biology of the Cell·Pauline M BennettJennifer C Pinder
Feb 24, 2006·Nature Genetics·Matthew StephensDeborah A Nickerson
May 31, 2006·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Brenda GerullLudwig Thierfelder
Aug 15, 2006·Clinica Chimica Acta; International Journal of Clinical Chemistry·Martin M LeWinterHenk L Granzier
Nov 6, 2007·Journal of the American College of Cardiology·Srijita Sen-ChowdhryWilliam J McKenna
May 15, 2008·The Journal of Physiological Sciences : JPS·Norio FukudaSatoshi Kurihara
Nov 6, 2008·Protein Expression and Purification·Julius BogomolovasGunter Stier
Apr 14, 2009·Lancet·Cristina BassoGaetano Thiene
Jun 27, 2009·Journal of Molecular and Cellular Cardiology·Marion Lewis Greaser
Jul 28, 2009·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·J D RobertsM H Gollob
Nov 3, 2009·Heart Rhythm : the Official Journal of the Heart Rhythm Society·J Peter van TintelenMaarten P van den Berg
Dec 25, 2009·Circulation. Cardiovascular Genetics·A Dénise den HaanDaniel P Judge
Apr 20, 2010·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Veronique FressartPhilippe Charron
Apr 29, 2010·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Ellen OttenJ Peter van Tintelen
May 19, 2010·Circulation·Martin M LeWinter, Henk L Granzier
Jun 17, 2010·Physiology·Wolfgang A Linke, Martina Krüger
Mar 3, 2011·European Heart Journal·Bruno PinamontiGianfranco Sinagra

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Family Health Status
Immunoglobulin Activity
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TTN gene
Myocardial Dysfunction
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