Truncations of Titin Causing Dilated Cardiomyopathy

• Published in: The New England journal of medicine Vol. 366; no. 7; pp. 619 - 628
• Main Authors: Herman, Daniel S, Lam, Lien, Taylor, Matthew R.G, Wang, Libin, Teekakirikul, Polakit, Christodoulou, Danos, Conner, Lauren, DePalma, Steven R, McDonough, Barbara, Sparks, Elizabeth, Teodorescu, Debbie Lin, Cirino, Allison L, Banner, Nicholas R, Pennell, Dudley J, Graw, Sharon, Merlo, Marco, Di Lenarda, Andrea, Sinagra, Gianfranco, Bos, J. Martijn, Ackerman, Michael J, Mitchell, Richard N, Murry, Charles E, Lakdawala, Neal K, Ho, Carolyn Y, Barton, Paul J.R, Cook, Stuart A, Mestroni, Luisa, Seidman, Christine E, Seidman, J.G
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 16.02.2012
• Subjects: Adult; Amino acids; Biological and medical sciences; Biomedical research; Cardiology. Vascular system; Cardiomyopathy; Cardiomyopathy, Dilated - genetics; Cardiomyopathy, Dilated - pathology; Connectin; Deoxyribonucleic acid; Dilated cardiomyopathy; DNA; Female; Frameshift mutation; General aspects; Genes; Genetic screening; Genomes; Genotyping Techniques; Health services; Heart; Hospitals; Humans; Insertion; Male; Medical sciences; Middle Aged; Muscle Proteins - genetics; Muscular dystrophy; Mutation; Myocarditis. Cardiomyopathies; Myocardium - pathology; Protein Kinases - genetics; Proteins; Sequence Analysis, DNA - methods; Sequence Deletion; Splicing; Womens health; United Kingdom > UK; Medicine; Connectin; Congestive hypertrophic cardiomyopathy; Dilated cardiomyopathy; Heart disease; Cardiovascular disease; Myocardial disease; Truncation
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1110186

Titin, an important protein in the sarcomere, is the largest human protein. This study identified mutations in the titin gene that result in a truncated protein as important causes of dilated cardiomyopathy. Gene mutation is an important cause of cardiomyopathy. Mutations in eight sarcomere-protein genes cause hypertrophic cardiomyopathy, detected in 40 to 70% of patients. 1 , 2 Variations in more than 40 genes, most of which encode components of the sarcomere, the cytoskeleton, or the nuclear lamina, have been shown or posited to cause dilated cardiomyopathy. 3 , 4 Clinical evaluation identifies 30 to 50% of patients with dilated cardiomyopathy as having a relative who is affected or likely to be affected, 5 – 7 implicating a genetic cause. However, pathogenic mutations have been found in only 20 to 30% of patients. 8 TTN, the gene encoding titin, . . .