titin's muscular dystrophy life expectancy
Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy, Hinze F, Dieterich C, Radke MH, Granzier H, Gotthardt M (2016), Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy, Iorga A, Cunningham CM, Moazeni S, Ruffenach G, Umar S, Eghbali M (2017), The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy, Jansweijer JA, Nieuwhof K, Russo F, Hoorntje ET, Jongbloed JD, Lekanne Deprez RH, Postma AV, Bronk M, van Rijsingen IA, de Haij S, Biagini E, van Haelst PL, van Wijngaarden J, van den Berg MP, Wilde AA, Mannens MM, de Boer RA, van Spaendonck-Zwarts KY, van Tintelen JP, Pinto YM (2017), Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy, Kellermayer D, Smith JE 3rd, Granzier H(2017), Knoll R, Hoshijima M, Hoffman HM, Person V, Lorenzen-Schmidt I, Bang ML, Hayashi T, Shiga N, Yasukawa H, Schaper W, McKenna W, Yokoyama M, Schork NJ, Omens JH, McCulloch AD, Kimura A, Gregorio CC, Poller W, Schaper J, Schultheiss HP, Chien KR (2002), The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy, Kolmerer B, Olivieri N, Witt CC, Herrmann BG, Labeit S (1996), Genomic organization of M line titin and its tissue-specific expression in two distinct isoforms, Kramerova I, Kudryashova E, Wu B, Ottenheijm C, Granzier H, Spencer MJ (2008), Novel role of calpain-3 in the triad-associated protein complex regulating calcium release in skeletal muscle, Kryczka KE, Dzielinska Z, Franaszczyk M, Wojtkowska I, Henzel J, Spiewak M, Stepinska J, Bilinska ZT, Ploski R, Demkow M (2018), Severe Course of Peripartum Cardiomyopathy and Subsequent Recovery in a Patient with a Novel TTN Gene-Truncating Mutation, Titins: giant proteins in charge of muscle ultrastructure and elasticity, Labeit S, Lahmers S, Burkart C, Fong C, McNabb M, Witt S, Witt C, Labeit D, Granzier H (2006), Expression of distinct classes of titin isoforms in striated and smooth muscles by alternative splicing, and their conserved interaction with filamins, TITINdb-a computational tool to assess titins role as a disease gene, Lahmers S, Wu Y, Call DR, Labeit S, Granzier H (2004), Developmental control of titin isoform expression and passive stiffness in fetal and neonatal myocardium, Lee EJ, Nedrud J, Schemmel P, Gotthardt M, Irving TC, Granzier HL (2013), Calcium sensitivity and myofilament lattice structure in titin N2B KO mice, The Role of Estrogen in Cardiac Metabolism and Diastolic Function, Titin Gene and Protein Functions in Passive and Active Muscle, Linschoten M, Teske AJ, Baas AF, Vink A, Dooijes D, Baars HF, Asselbergs FW (2017), Truncating Titin (TTN) Variants in Chemotherapy-Induced Cardiomyopathy, Methawasin M, Hutchinson KR, Lee EJ, Smith JE 3rd, Saripalli C, Hidalgo CG, Ottenheijm CA, Granzier H (2014), Experimentally increasing titin compliance in a novel mouse model attenuates the Frank-Starling mechanism but has a beneficial effect on diastole, Methawasin M, Strom JG, Slater RE, Fernandez V, Saripalli C, Granzier H (2016), Experimentally Increasing the Compliance of Titin Through RNA Binding Motif-20 (RBM20) Inhibition Improves Diastolic Function In a Mouse Model of Heart Failure With Preserved Ejection Fraction, Moriscot AS, Baptista IL, Bogomolovas J, Witt C, Hirner S, Granzier H, Labeit S (2010), MuRF1 is a muscle fiber-type II associated factor and together with MuRF2 regulates type-II fiber trophicity and maintenance, Muhle-Goll C, Habeck M, Cazorla O, Nilges M, Labeit S, Granzier H (2001), Structural and functional studies of titins fn3 modules reveal conserved surface patterns and binding to myosin S1--a possible role in the Frank-Starling mechanism of the heart, Musa H, Meek S, Gautel M, Peddie D, Smith AJ, Peckham M (2006), Targeted homozygous deletion of M-band titin in cardiomyocytes prevents sarcomere formation, Nagueh SF, Shah G, Wu Y, Torre-Amione G, King NM, Lahmers S, Witt CC, Becker K, Labeit S, Granzier HL (2004), Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy, Neagoe C, Kulke M, del Monte F, Gwathmey JK, de Tombe PP, Hajjar RJ, Linke WA (2002), Titin isoform switch in ischemic human heart disease, Norton N, Li D, Rampersaud E, Morales A, Martin ER, Zuchner S, Guo S, Gonzalez M, Hedges DJ, Robertson PD, Krumm N, Nickerson DA, Hershberger RE, National Heart L, Blood Institute GOESP, the Exome Sequencing Project Family Studies Project T (2013), Exome sequencing and genome-wide linkage analysis in 17 families illustrate the complex contribution of TTN truncating variants to dilated cardiomyopathy, Oates EC, Jones KJ, Donkervoort S, Charlton A, Brammah S, Smith JE 3rd, Ware JS, Yau KS, Swanson LC, Whiffin N, Peduto AJ, Bournazos A, Waddell LB, Farrar MA, Sampaio HA, Teoh HL, Lamont PJ, Mowat D, Fitzsimons RB, Corbett AJ, Ryan MM, OGrady GL, Sandaradura SA, Ghaoui R, Joshi H, Marshall JL, Nolan MA, Kaur S, Punetha J, Topf A, Harris E, Bakshi M, Genetti CA, Marttila M, Werlauff U, Streichenberger N, Pestronk A, Mazanti I, Pinner JR, Vuillerot C, Grosmann C, Camacho A, Mohassel P, Leach ME, Foley AR, Bharucha-Goebel D, Collins J, Connolly AM, Gilbreath HR, Iannaccone ST, Castro D, Cummings BB, Webster RI, Lazaro L, Vissing J, Coppens S, Deconinck N, Luk HM, Thomas NH, Foulds NC, Illingworth MA, Ellard S, McLean CA, Phadke R, Ravenscroft G, Witting N, Hackman P, Richard I, Cooper ST, Kamsteeg EJ, Hoffman EP, Bushby K, Straub V, Udd B, Ferreiro A, North KN, Clarke NF, Lek M, Beggs AH, Bonnemann CG, MacArthur DG, Granzier H, Davis MR, Laing NG (2018), Congenital Titinopathy: Comprehensive characterization and pathogenic insights, Ojima K, Kawabata Y, Nakao H, Nakao K, Doi N, Kitamura F, Ono Y, Hata S, Suzuki H, Kawahara H, Bogomolovas J, Witt C, Ottenheijm C, Labeit S, Granzier H, Toyama-Sorimachi N, Sorimachi M, Suzuki K, Maeda T, Abe K, Aiba A, Sorimachi H (2010), Dynamic distribution of muscle-specific calpain in mice has a key role in physical-stress adaptation and is impaired in muscular dystrophy, Role of titin in skeletal muscle function and disease, Peng J, Raddatz K, Labeit S, Granzier H, Gotthardt M (2005), Muscle atrophy in titin M-line deficient mice, Peng J, Raddatz K, Molkentin JD, Wu Y, Labeit S, Granzier H, Gotthardt M (2007), Cardiac hypertrophy and reduced contractility in hearts deficient in the titin kinase region, Perkin J, Slater R, Del Favero G, Lanzicher T, Hidalgo C, Anderson B, Smith JE 3rd, Sbaizero O, Labeit S, Granzier H (2015), Phosphorylating Titins Cardiac N2B Element by ERK2 or CaMKIIdelta Lowers the Single Molecule and Cardiac Muscle Force, Radke MH, Peng J, Wu Y, McNabb M, Nelson OL, Granzier H, Gotthardt M (2007), Targeted deletion of titin N2B region leads to diastolic dysfunction and cardiac atrophy, Radke MH, Polack C, Methawasin M, Fink C, Granzier HL, Gotthardt M (2019), Deleting Full Length Titin Versus the Titin M-Band Region Leads to Differential Mechanosignaling and Cardiac Phenotypes, Raskin A, Lange S, Banares K, Lyon RC, Zieseniss A, Lee LK, Yamazaki KG, Granzier HL, Gregorio CC, McCulloch AD, Omens JH, Sheikh F (2012), A novel mechanism involving four-and-a-half LIM domain protein-1 and extracellular signal-regulated kinase-2 regulates titin phosphorylation and mechanics, Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, Buchan RJ, Walsh R, John S, Wilkinson S, Mazzarotto F, Felkin LE, Gong S, MacArthur JA, Cunningham F, Flannick J, Gabriel SB, Altshuler DM, Macdonald PS, Heinig M, Keogh AM, Hayward CS, Banner NR, Pennell DJ, ORegan DP, San TR, de Marvao A, Dawes TJ, Gulati A, Birks EJ, Yacoub MH, Radke M, Gotthardt M, Wilson JG, ODonnell CJ, Prasad SK, Barton PJ, Fatkin D, Hubner N, Seidman JG, Seidman CE, Cook SA (2015), Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease, Roncarati R, Viviani Anselmi C, Krawitz P, Lattanzi G, von Kodolitsch Y, Perrot A, di Pasquale E, Papa L, Portararo P, Columbaro M, Forni A, Faggian G, Condorelli G, Robinson PN (2013), Doubly heterozygous LMNA and TTN mutations revealed by exome sequencing in a severe form of dilated cardiomyopathy, Savarese M, Sarparanta J, Vihola A, Udd B, Hackman P (2016), Increasing Role of Titin Mutations in Neuromuscular Disorders, Schafer S, de Marvao A, Adami E, Fiedler LR, Ng B, Khin E, Rackham OJ, van Heesch S, Pua CJ, Kui M, Walsh R, Tayal U, Prasad SK, Dawes TJ, Ko NS, Sim D, Chan LL, Chin CW, Mazzarotto F, Barton PJ, Kreuchwig F, de Kleijn DP, Totman T, Biffi C, Tee N, Rueckert D, Schneider V, Faber A, Regitz-Zagrosek V, Seidman JG, Seidman CE, Linke WA, Kovalik JP, ORegan D, Ware JS, Hubner N, Cook SA (2017), Titin-truncating variants affect heart function in disease cohorts and the general population, Schick R, Mekies LN, Shemer Y, Eisen B, Hallas T, Ben Jehuda R, Ben-Ari M, Szantai A, Willi L, Shulman R, Gramlich M, Pane LS, My I, Freimark D, Murgia M, Santamaria G, Gherghiceanu M, Arad M, Moretti A, Binah O (2018), Functional abnormalities in induced Pluripotent Stem Cell-derived cardiomyocytes generated from titin-mutated patients with dilated cardiomyopathy, Siegfried JD, Morales A, Kushner JD, Burkett E, Cowan J, Mauro AC, Huggins GS, Li D, Norton N, Hershberger RE (2013), Return of genetic results in the familial dilated cardiomyopathy research project, Taylor M, Graw S, Sinagra G, Barnes C, Slavov D, Brun F, Pinamonti B, Salcedo EE, Sauer W, Pyxaras S, Anderson B, Simon B, Bogomolovas J, Labeit S, Granzier H, Mestroni L (2011), Genetic variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes, Tonino P, Kiss B, Strom J, Methawasin M, Smith JE 3rd, Kolb J, Labeit S, Granzier H (2017), The giant protein titin regulates the length of the striated muscle thick filament, The mechanically active domain of titin in cardiac muscle, Trombitas K, Wu Y, Labeit D, Labeit S, Granzier H (2001), Cardiac titin isoforms are coexpressed in the half-sarcomere and extend independently, Properties of titin immunoglobulin and fibronectin-3 domains, UniProt: a worldwide hub of protein knowledge, van Spaendonck-Zwarts KY, Posafalvi A, van den Berg MP, Hilfiker-Kleiner D, Bollen IA, Sliwa K, Alders M, Almomani R, van Langen IM, van der Meer P, Sinke RJ, van der Velden J, Van Veldhuisen DJ, van Tintelen JP, Jongbloed JD (2014), Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy, Verdonschot JAJ, Hazebroek MR, Derks KWJ, Barandiaran Aizpurua A, Merken JJ, Wang P, Bierau J, van den Wijngaard A, Schalla SM, Abdul Hamid MA, van Bilsen M, van Empel VPM, Knackstedt C, Brunner-La Rocca HP, Brunner HG, Krapels IPC, Heymans SRB (2018), Titin cardiomyopathy leads to altered mitochondrial energetics, increased fibrosis and long-term life-threatening arrhythmias, Role of titin in cardiomyopathy: from DNA variants to patient stratification, Ware JS, Li J, Mazaika E, Yasso CM, DeSouza T, Cappola TP, Tsai EJ, Hilfiker-Kleiner D, Kamiya CA, Mazzarotto F, Cook SA, Halder I, Prasad SK, Pisarcik J, Hanley-Yanez K, Alharethi R, Damp J, Hsich E, Elkayam U, Sheppard R, Kealey A, Alexis J, Ramani G, Safirstein J, Boehmer J, Pauly DF, Wittstein IS, Thohan V, Zucker MJ, Liu P, Gorcsan J 3rd, McNamara DM, Seidman CE, Seidman JG, Arany Z, Imac, Investigators I (2016), Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies, Watanabe K, Muhle-Goll C, Kellermayer MS, Labeit S, Granzier H (2002), Different molecular mechanics displayed by titins constitutively and differentially expressed tandem Ig segments, Witt CC, Ono Y, Puschmann E, McNabb M, Wu Y, Gotthardt M, Witt SH, Haak M, Labeit D, Gregorio CC, Sorimachi H, Granzier H, Labeit S (2004), Induction and myofibrillar targeting of CARP, and suppression of the Nkx2.5 pathway in the MDM mouse with impaired titin-based signaling, Witt SH, Granzier H, Witt CC, Labeit S (2005), MURF-1 and MURF-2 target a specific subset of myofibrillar proteins redundantly: towards understanding MURF-dependent muscle ubiquitination, Witt SH, Labeit D, Granzier H, Labeit S, Witt CC (2005), Dimerization of the cardiac ankyrin protein CARP: implications for MARP titin-based signaling, Wu Y, Bell SP, Trombitas K, Witt CC, Labeit S, LeWinter MM, Granzier H (2002), Changes in titin isoform expression in pacing-induced cardiac failure give rise to increased passive muscle stiffness, Wu Y, Cazorla O, Labeit D, Labeit S, Granzier H (2000), Changes in titin and collagen underlie diastolic stiffness diversity of cardiac muscle, Wu Y, Labeit S, Lewinter MM, Granzier H (2002), Titin: an endosarcomeric protein that modulates myocardial stiffness in DCM, Wu Y, Peng J, Campbell KB, Labeit S, Granzier H (2007), Hypothyroidism leads to increased collagen-based stiffness and re-expression of large cardiac titin isoforms with high compliance, Yamasaki R, Wu Y, McNabb M, Greaser M, Labeit S, Granzier H (2002), Protein kinase A phosphorylates titins cardiac-specific N2B domain and reduces passive tension in rat cardiac myocytes, Yano T, Shimoshige S, Miki T, Tanno M, Mochizuki A, Fujito T, Yuda S, Muranaka A, Ogasawara M, Hashimoto A, Tsuchihashi K, Miura T (2016), Clinical impact of myocardial mTORC1 activation in nonischemic dilated cardiomyopathy, Zou J, Tran D, Baalbaki M, Tang LF, Poon A, Pelonero A, Titus EW, Yuan C, Shi C, Patchava S, Halper E, Garg J, Movsesyan I, Yin C, Wu R, Wilsbacher LD, Liu J, Hager RL, Coughlin SR, Jinek M, Pullinger CR, Kane JP, Hart DO, Kwok PY, Deo RC (2015), An internal promoter underlies the difference in disease severity between N- and C-terminal truncation mutations of Titin in zebrafish. The site is secure. P, Marchand Although further studies are needed to attribute causality to missense changes, reporting possible causative variants is an effective strategy to improve consistency in the interpretation of molecular findings in titin. MD is a progressive condition, which means it gets worse over time. et al. . T, Fanin The .gov means its official. et al. M13 primers were used to perform Sanger sequencing using an ABI PRISM 3130XL Genetic Analyzer (Applied Biosystems). O, Verellen Unable to load your collection due to an error, Unable to load your delegates due to an error. Novel heterozygous truncating titin variants affecting the A-band are associated with cardiomyopathy and myopathy/muscular dystrophy. The A-band segment of titin contains 178 Ig and Fn3 domains and is functionally inextensible [69,106,16]. By continuing to use our site, or clicking "Continue," you are agreeing to our, Figure 1. The amino acid change probably affects the folding of the domain (Figure 2). B, Hackman A, Haravuori Terms of Use| Schafer et. et al. Love Teen Mom? The clinical interpretation of mutations in exon 364, previously associated with TMD (like the p.Ile35947Asn in patient III), is more complex. TTNtv have also been linked to peripartum cardiomyopathy (PPCM) where the distribution of truncating variants in PPCM is similar to that found in DCM [108,112]. B, Hackman In this case series, 504 patients with skeletal muscle disorders were screened with a targeted resequencing approach. government site. First, we enrolled, in a multicenter study, patients with clinically and genetically heterogenous conditions and specific clinical studies (magnetic resonance imaging or cardiac tests) were unavailable or not performed for some patients. Since we first met Leah Messer nearly a decade ago, the Teen Mom 2 star has taken us along for the emotional and inspiring journey of her daughter Aliannahs battle with muscular dystrophy. Muscular Dystrophy Life Expectancy. The IA zone is near the ends of the thick filaments and is striking in that the regular domain patterns of Ig and Fnlll domains is broken with a stretch of 6 Fnlll domains that is found preceding the D zone. Accession numbers for the Metatranscript and Novex-3 proteins are {"type":"entrez-protein","attrs":{"text":"NP_001254479","term_id":"642945631"}}NP_001254479 and NP 596870.
