Titin mutations as the molecular basis for dilated cardiomyopathy

Biochemical and Biophysical Research Communications
Manatsu Itoh-SatohAkinori Kimura


Dilated cardiomyopathy (DCM) is a heterogeneous cardiac disease characterized by ventricular dilatation and systolic dysfunction. Recent genetic studies have revealed that mutations in genes for cardiac sarcomere components lead to DCM. The cardiac sarcomere consists of thick and thin filaments and a giant protein, titin. Because one of the loci of familial DCM was mapped to the region of the titin gene, we searched for titin mutations in the patients and identified four possible disease-associated mutations. Two mutations, Val54Met and Ala743Val, were found in the Z-line region of titin and decreased binding affinities of titin to Z-line proteins T-cap/telethonin and alpha-actinin, respectively, in yeast two-hybrid assays. The other two mutations were found in the cardiac-specific N2-B region of titin and one of them was a nonsense mutation, Glu4053ter, presumably encoding for a truncated nonfunctional molecule. These observations suggest that titin mutations may cause DCM in a subset of the patients.


Mar 2, 2011·Journal of Cardiovascular Translational Research·Byambajav BuyandelgerRalph Knöll
Aug 16, 2012·European Journal of Human Genetics : EJHG·T MeyerGerman Competence Network Heart Failure
Mar 7, 2013·European Journal of Human Genetics : EJHG·Roberta RoncaratiPeter N Robinson
Apr 3, 2012·Nature Medicine·Wei GuoMichael Gotthardt
Dec 7, 2007·Cardiovascular Research·Sachio Morimoto
Oct 30, 2008·Human Molecular Genetics·Jeffrey R GuyonLouis M Kunkel
Jul 20, 2010·Human Molecular Genetics·Mark EijgelsheimChristopher J O'Donnell
Aug 28, 2012·Nucleic Acids Research·Elke SchaperMaria Anisimova
Feb 27, 2010·Current Opinion in Cardiology·Lisa Dellefave, Elizabeth M McNally
Dec 10, 2008·Genome Research·Frauke FriedrichsMonika Stoll
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Kathleen A ClarkCarol C Gregorio
Jul 27, 2002·Annual Review of Genomics and Human Genetics·Jordan T Shin, Mark C Fishman
Oct 1, 2009·Physiological Reviews·Aikaterini Kontrogianni-KonstantopoulosRobert J Bloch
Jul 26, 2012·Biochemistry Research International·Ruti Parvari, Aviva Levitas
Feb 27, 2013·Circulation·Martin LeWinter, Henk Granzier
Jan 18, 2003·The Journal of Clinical Investigation·Kenneth R Chien
Mar 6, 2012·BMC Bioinformatics·Donny SohLimsoon Wong
Oct 24, 2007·BMC Veterinary Research·Anje C WiersmaJoanna Dukes-McEwan
Sep 6, 2008·Circulation Journal : Official Journal of the Japanese Circulation Society·Akinori Kimura
Nov 19, 2008·Circulation Journal : Official Journal of the Japanese Circulation Society·Takuro ArimuraAkinori Kimura
May 28, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Akinori Kimura
Sep 28, 2013·Journal of Cardiovascular Pharmacology·Martin LeWinter, Henk Granzier
Nov 1, 2007·Future Cardiology·Derk FrankN Frey
May 13, 2014·Neuromuscular Disorders : NMD·Jeremy RouillonFedor Svinartchouk
Oct 10, 2013·Human Molecular Genetics·Claire ChauveauAna Ferreiro
May 21, 2013·Current Cardiology Reports·Ana Morales, Ray E Hershberger
Jan 18, 2006·Heart Failure Reviews·Audrey N Chang, James D Potter
Jan 18, 2006·Heart Failure Reviews·Henk GranzierMartin LeWinter
Jul 13, 2002·Trends in Molecular Medicine·Stefan Hein, Jutta Schaper
Jun 3, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·W PollerH-P Schultheiss
May 31, 2006·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Brenda GerullLudwig Thierfelder
Apr 6, 2012·The American Journal of Cardiology·Guy YoskovitzDov Freimark
Jul 30, 2009·Journal of Molecular and Cellular Cardiology·Martina Krüger, Wolfgang A Linke


Oct 15, 1992·Biochemical and Biophysical Research Communications·H NishiT Sasazuki
Oct 13, 1995·Science·Siegfried Labeit, B Kolmerer
Oct 1, 1995·Journal of Molecular and Cellular Cardiology·H NishiAkinori Kimura
Apr 1, 1996·Nature Genetics·S BioneD Toniolo
Nov 14, 1997·FEBS Letters·G ValleG Lanfranchi
Mar 4, 1998·Current Opinion in Cell Biology·Jeffrey A Towbin
Mar 2, 1999·Circulation·B L SiuChristine Seidman
Aug 27, 1999·Biochemical and Biophysical Research Communications·M SatohAkinori Kimura
Sep 7, 2000·The Journal of Clinical Investigation·S TsubataJeffrey A Towbin
Oct 29, 2000·European Heart Journal·Calum A MacRae
Dec 7, 2000·The New England Journal of Medicine·M KamisagoChristine Seidman
Jul 10, 2001·American Journal of Human Genetics·J Schönberger, Christine Seidman

Related Concepts

Cardiomyopathy, Familial Idiopathic
Yeast Two-Hybrid System Techniques
Mutation, Nonsense
TCAP gene
Tertiary Protein Structure
TTN gene
Protein KINASE
Z Line
Dilated Cardiomyopathy Pathway

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