Skip to main content
SpringerLink
Log in
Book cover

Genetic Causes of Cardiac Disease pp 45–91Cite as

The Genetic Landscape of Cardiomyopathies

  • Chapter
  • First Online:

Part of the book series: Cardiac and Vascular Biology ((Abbreviated title: Card. vasc. biol.,volume 7))

Abstract

Insights into genetic causes of cardiomyopathies have tremendously contributed to the understanding of the molecular basis and pathophysiology of hypertrophic, dilated, arrhythmogenic, restrictive and left ventricular noncompaction cardiomyopathy. More than thousand mutations in approximately 100 genes encoding proteins involved in many different subcellular systems have been identified indicating the diversity of pathways contributing to pathological cardiac remodeling. Moreover, the classical view based on morphology and physiology has been shifted toward genetic and molecular patterns defining the etiology of cardiomyopathies. Today, novel high-throughput genetic technologies provide an opportunity to diagnose individuals based on their genetic findings, sometimes before clinical signs of the disease occur. However, the challenge remains that rapid research developments and the complexity of genetic information are getting introduced into the clinical practice, which requires dedicated guidance in genetic counselling and interpretation of genetic test results for the management of families with inherited cardiomyopathies.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006;113(14):1807–16. https://doi.org/10.1161/CIRCULATIONAHA.106.174287.

    Article  PubMed  Google Scholar 

  2. Geisterfer-Lowrance AAT, Kass S, Tanigawa G, Vosberg H-P, McKenna W, Seidman CE, Seidman JG. A molecular basis for familial hypertrophic cardiomyopathy: a β cardiac myosin heavy chain gene missense mutation. Cell. 1990;62(5):999–1006. https://doi.org/10.1016/0092-8674(90)90274-I.

    Article  CAS  PubMed  Google Scholar 

  3. Ho CY, Charron P, Richard P, Girolami F, Van Spaendonck-Zwarts KY, Pinto Y. Genetic advances in sarcomeric cardiomyopathies: state of the art. Cardiovasc Res. 2015;105(4):397–408. https://doi.org/10.1093/cvr/cvv025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, et al. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet. 2004;36(11):1162–4. https://doi.org/10.1038/ng1461.

    Article  CAS  PubMed  Google Scholar 

  5. McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A, et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet (London, England). 2000;355(9221):2119–24.

    Article  CAS  Google Scholar 

  6. Genomes Project, C, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, et al. A map of human genome variation from population-scale sequencing. Nature. 2010;467(7319):1061–73. https://doi.org/10.1038/nature09534.

    Article  CAS  Google Scholar 

  7. Golbus JR, Puckelwartz MJ, Dellefave-Castillo L, Fahrenbach JP, Nelakuditi V, Pesce LL, et al. Targeted analysis of whole genome sequence data to diagnose genetic cardiomyopathy. Circ Cardiovasc Genet. 2014;7(6):751–9. https://doi.org/10.1161/CIRCGENETICS.113.000578.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kayvanpour E, Sedaghat-Hamedani F, Amr A, Lai A, Haas J, Holzer DB, et al. Genotype-phenotype associations in dilated cardiomyopathy: meta-analysis on more than 8000 individuals. Clin Res Cardiol. 2017;106(2):127–39. https://doi.org/10.1007/s00392-016-1033-6.

    Article  CAS  PubMed  Google Scholar 

  9. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–23. https://doi.org/10.1038/gim.2015.30.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic Analysis of 4111 Subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation. 1995;92(4):785–9. https://doi.org/10.1161/01.cir.92.4.785.

    Article  CAS  PubMed  Google Scholar 

  11. Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35(39):2733–79. https://doi.org/10.1093/eurheartj/ehu284.

    Article  PubMed  Google Scholar 

  12. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, et al. ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;58(25):e212–60. https://doi.org/10.1016/j.jacc.2011.06.011.

    Article  CAS  PubMed  Google Scholar 

  13. Nagueh SF, Mahmarian JJ. Noninvasive cardiac imaging in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2006;48(12):2410–22. https://doi.org/10.1016/j.jacc.2006.07.065.

    Article  PubMed  Google Scholar 

  14. Maron BJ, Rowin EJ, Casey SA, Garberich RF, Maron MS. What do patients with hypertrophic cardiomyopathy die from? Am J Cardiol. 2016a;117(3):434–5. https://doi.org/10.1016/j.amjcard.2015.11.013.

    Article  PubMed  Google Scholar 

  15. Maron BJ, Rowin EJ, Casey SA, Lesser JR, Garberich RF, McGriff DM, Maron MS. Hypertrophic cardiomyopathy in children, adolescents, and young adults associated with low cardiovascular mortality with contemporary management strategies. Circulation. 2016b;133(1):62–73. https://doi.org/10.1161/circulationaha.115.017633.

    Article  PubMed  Google Scholar 

  16. Maron BJ, Rowin EJ, Casey SA, Link MS, Lesser JR, Chan RH, et al. Hypertrophic cardiomyopathy in adulthood associated with low cardiovascular mortality with contemporary management strategies. J Am Coll Cardiol. 2015;65(18):1915–28. https://doi.org/10.1016/j.jacc.2015.02.061.

    Article  PubMed  Google Scholar 

  17. Charron P, Carrier L, Dubourg O, Tesson F, Desnos M, Richard P, et al. Penetrance of familial hypertrophic cardiomyopathy. Genet Couns. 1997;8(2):107–14.

    CAS  PubMed  Google Scholar 

  18. Ingles J, Doolan A, Chiu C, Seidman J, Seidman C, Semsarian C. Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling. J Med Genet. 2005;42(10):e59. https://doi.org/10.1136/jmg.2005.033886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA. 2002;287(10):1308–20.

    Article  PubMed  Google Scholar 

  20. Niimura H, Bachinski LL, Sangwatanaroj S, Watkins H, Chudley AE, McKenna W, et al. Mutations in the gene for cardiac myosin-binding protein c and late-onset familial hypertrophic cardiomyopathy. N Engl J Med. 1998;338(18):1248–57. https://doi.org/10.1056/nejm199804303381802.

    Article  CAS  PubMed  Google Scholar 

  21. Page SP, Kounas S, Syrris P, Christiansen M, Frank-Hansen R, Andersen PS, et al. Cardiac myosin binding protein-C mutations in families with hypertrophic cardiomyopathy: disease expression in relation to age, gender, and long term outcome. Circ Cardiovasc Genet. 2012;5(2):156–66. https://doi.org/10.1161/circgenetics.111.960831.

    Article  CAS  PubMed  Google Scholar 

  22. Golbus JR, Puckelwartz MJ, Fahrenbach JP, Dellefave-Castillo LM, Wolfgeher D, McNally EM. Population-based variation in cardiomyopathy genes. Circ Cardiovasc Genet. 2012;5(4):391–9. https://doi.org/10.1161/CIRCGENETICS.112.962928.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg H-P, et al. α-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell. 1994;77(5):701–12. https://doi.org/10.1016/0092-8674(94)90054-X.

    Article  PubMed  Google Scholar 

  24. Watkins H, Conner D, Thierfelder L, Jarcho JA, MacRae C, McKenna WJ, et al. Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy. Nat Genet. 1995;11(4):434–7.

    Article  CAS  PubMed  Google Scholar 

  25. Bonne G, Carrier L, Bercovici J, Cruaud C, Richard P, Hainque B, et al. Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy. Nat Genet. 1995;11(4):438–40.

    Article  CAS  PubMed  Google Scholar 

  26. Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, et al. Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nat Genet. 1996;13(1):63–9.

    Article  CAS  PubMed  Google Scholar 

  27. Kimura A, Harada H, Park J-E, Nishi H, Satoh M, Takahashi M, et al. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nat Genet. 1997;16(4):379–82.

    Article  CAS  PubMed  Google Scholar 

  28. Mogensen J, Klausen IC, Pedersen AK, Egeblad H, Bross P, Kruse TA, et al. α-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy. J Clin Invest. 1999;103(10):R39–43. https://doi.org/10.1172/JCI6460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Andersen PS, Havndrup O, Hougs L, Sørensen KM, Jensen M, Larsen LA, et al. Diagnostic yield, interpretation, and clinical utility of mutation screening of sarcomere encoding genes in Danish hypertrophic cardiomyopathy patients and relatives. Hum Mutat. 2009;30(3):363–70. https://doi.org/10.1002/humu.20862.

    Article  CAS  PubMed  Google Scholar 

  30. Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, et al. Hypertrophic cardiomyopathy. Distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation. 2003;107(17):2227–32. https://doi.org/10.1161/01.cir.0000066323.15244.54.

    Article  PubMed  Google Scholar 

  31. Burke MA, Cook SA, Seidman JG, Seidman CE. Clinical and mechanistic insights into the genetics of cardiomyopathy. J Am Coll Cardiol. 2016;68(25):2871–86. https://doi.org/10.1016/j.jacc.2016.08.079.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Knoll R, Buyandelger B, Lab M. The sarcomeric Z-disc and Z-discopathies. J Biomed Biotechnol. 2011;2011:569628. https://doi.org/10.1155/2011/569628.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Landstrom AP, Ackerman MJ. Beyond the cardiac myofilament: hypertrophic cardiomyopathy-associated mutations in genes that encode calcium-handling proteins. Curr Mol Med. 2012;12(5):507–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Millat G, Bouvagnet P, Chevalier P, Dauphin C, Simon Jouk P, Da Costa A, et al. Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy. Eur J Med Genet. 2010;53(5):261–7. https://doi.org/10.1016/j.ejmg.2010.07.007.

    Article  PubMed  Google Scholar 

  35. Anan R, Greve G, Thierfelder L, Watkins H, McKenna WJ, Solomon S, et al. Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy. J Clin Invest. 1994;93(1):280–5. https://doi.org/10.1172/JCI116957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pasquale F, Syrris P, Kaski JP, Mogensen J, McKenna WJ, Elliott P. Long-term outcomes in hypertrophic cardiomyopathy caused by mutations in the cardiac troponin T gene. Circ Cardiovasc Genet. 2012;5(1):10–7. https://doi.org/10.1161/circgenetics.111.959973.

    Article  CAS  PubMed  Google Scholar 

  37. Alpert NR, Mohiddin SA, Tripodi D, Jacobson-Hatzell J, Vaughn-Whitley K, Brosseau C, et al. Molecular and phenotypic effects of heterozygous, homozygous, and compound heterozygote myosin heavy-chain mutations. Am J Physiol Heart Circ Physiol. 2005;288(3):H1097–102. https://doi.org/10.1152/ajpheart.00650.2004.

    Article  CAS  PubMed  Google Scholar 

  38. Fourey D, Care M, Siminovitch KA, Weissler-Snir A, Hindieh W, Chan RH, et al. Prevalence and clinical implication of double mutations in hypertrophic cardiomyopathy: revisiting the gene-dose effect. Circ Cardiovasc Genet. 2017;10(2):e001685. https://doi.org/10.1161/circgenetics.116.001685.

    Article  CAS  PubMed  Google Scholar 

  39. Olivotto I, d’Amati G, Basso C, Van Rossum A, Patten M, Emdin M, et al. Defining phenotypes and disease progression in sarcomeric cardiomyopathies: contemporary role of clinical investigations. Cardiovasc Res. 2015;105(4):409–23. https://doi.org/10.1093/cvr/cvv024.

    Article  CAS  PubMed  Google Scholar 

  40. Charron P, Arad M, Arbustini E, Basso C, Bilinska Z, Elliott P, et al. Genetic counselling and testing in cardiomyopathies: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2010;31(22):2715–26. https://doi.org/10.1093/eurheartj/ehq271.

    Article  PubMed  Google Scholar 

  41. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008;29(2):270–6. https://doi.org/10.1093/eurheartj/ehm342.

    Article  PubMed  Google Scholar 

  42. Andreasen C, Nielsen JB, Refsgaard L, Holst AG, Christensen AH, Andreasen L, et al. New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Eur J Hum Genet. 2013;21(9):918–28. https://doi.org/10.1038/ejhg.2012.283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lopes LR, Zekavati A, Syrris P, Hubank M, Giambartolomei C, Dalageorgou C, et al. Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing. J Med Genet. 2013;50(4):228–39. https://doi.org/10.1136/jmedgenet-2012-101270.

    Article  CAS  PubMed  Google Scholar 

  44. Colan SD, Lipshultz SE, Lowe AM, Sleeper LA, Messere J, Cox GF, et al. Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry. Circulation. 2007;115(6):773–81. https://doi.org/10.1161/circulationaha.106.621185.

    Article  PubMed  Google Scholar 

  45. Rapezzi C, Arbustini E, Caforio AL, Charron P, Gimeno-Blanes J, Helio T, et al. Diagnostic work-up in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013;34(19):1448–58. https://doi.org/10.1093/eurheartj/ehs397.

    Article  PubMed  Google Scholar 

  46. Sata M, Ikebe M. Functional analysis of the mutations in the human cardiac beta-myosin that are responsible for familial hypertrophic cardiomyopathy. Implication for the clinical outcome. J Clin Invest. 1996;98(12):2866–73. https://doi.org/10.1172/jci119115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Harris SP, Lyons RG, Bezold KL. In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament. Circ Res. 2011;108(6):751–64. https://doi.org/10.1161/circresaha.110.231670.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. van Dijk SJ, Dooijes D, dos Remedios C, Michels M, Lamers JMJ, Winegrad S, et al. Cardiac myosin-binding protein C mutations and hypertrophic cardiomyopathy. Haploinsufficiency, deranged phosphorylation, and cardiomyocyte dysfunction. Circulation. 2009;119(11):1473–83. https://doi.org/10.1161/circulationaha.108.838672.

    Article  PubMed  Google Scholar 

  49. Robinson P, Griffiths PJ, Watkins H, Redwood CS. Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments. Circ Res. 2007;101(12):1266–73. https://doi.org/10.1161/circresaha.107.156380.

    Article  CAS  PubMed  Google Scholar 

  50. Robinson P, Mirza M, Knott A, Abdulrazzak H, Willott R, Marston S, et al. Alterations in thin filament regulation induced by a human cardiac troponin T mutant that causes dilated cardiomyopathy are distinct from those induced by troponin T mutants that cause hypertrophic cardiomyopathy. J Biol Chem. 2002;277(43):40710–6. https://doi.org/10.1074/jbc.M203446200.

    Article  CAS  PubMed  Google Scholar 

  51. Guinto PJ, Haim TE, Dowell-Martino CC, Sibinga N, Tardiff JC. Temporal and mutation-specific alterations in Ca2+ homeostasis differentially determine the progression of cTnT-related cardiomyopathies in murine models. Am J Physiol Heart Circ Physiol. 2009;297(2):H614–26. https://doi.org/10.1152/ajpheart.01143.2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ashrafian H, McKenna WJ, Watkins H. Disease pathways and novel therapeutic targets in hypertrophic cardiomyopathy. Circ Res. 2011;109(1):86–96. https://doi.org/10.1161/circresaha.111.242974.

    Article  CAS  PubMed  Google Scholar 

  53. Spudich JA. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases. Biophys J. 2014;106(6):1236–49. https://doi.org/10.1016/j.bpj.2014.02.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kirschner SE, Becker E, Antognozzi M, Kubis HP, Francino A, Navarro-Lopez F, et al. Hypertrophic cardiomyopathy-related beta-myosin mutations cause highly variable calcium sensitivity with functional imbalances among individual muscle cells. Am J Physiol Heart Circ Physiol. 2005;288(3):H1242–51. https://doi.org/10.1152/ajpheart.00686.2004.

    Article  CAS  PubMed  Google Scholar 

  55. Green EM, Wakimoto H, Anderson RL, Evanchik MJ, Gorham JM, Harrison BC, et al. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science. 2016;351(6273):617–21. https://doi.org/10.1126/science.aad3456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Grunig E, Tasman JA, Kucherer H, Franz W, Kubler W, Katus HA. Frequency and phenotypes of familial dilated cardiomyopathy. J Am Coll Cardiol. 1998;31(1):186–94.

    Article  CAS  PubMed  Google Scholar 

  57. Petretta M, Pirozzi F, Sasso L, Paglia A, Bonaduce D. Review and metaanalysis of the frequency of familial dilated cardiomyopathy. Am J Cardiol. 2011;108(8):1171–6. https://doi.org/10.1016/j.amjcard.2011.06.022.

    Article  PubMed  Google Scholar 

  58. Pinto YM, Elliott PM, Arbustini E, Adler Y, Anastasakis A, Bohm M, et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J. 2016;37(23):1850–8. https://doi.org/10.1093/eurheartj/ehv727.

    Article  PubMed  Google Scholar 

  59. Codd MB, Sugrue DD, Gersh BJ, Melton LJ. Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy. A population-based study in Olmsted County, Minnesota, 1975–1984. Circulation. 1989;80(3):564–72. https://doi.org/10.1161/01.cir.80.3.564.

    Article  CAS  PubMed  Google Scholar 

  60. Schafer S, de Marvao A, Adami E, Fiedler LR, Ng B, Khin E, et al. Titin-truncating variants affect heart function in disease cohorts and the general population. Nat Genet. 2017;49(1):46–53. https://doi.org/10.1038/ng.3719.. http://www.nature.com/ng/journal/v49/n1/abs/ng.3719.html#supplementary-information

    Article  CAS  PubMed  Google Scholar 

  61. Gulati A, Jabbour A, Ismail TF, Guha K, Khwaja J, Raza S, et al. Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA. 2013;309(9):896–908. https://doi.org/10.1001/jama.2013.1363.

    Article  CAS  PubMed  Google Scholar 

  62. Kober L, Thune JJ, Nielsen JC, Haarbo J, Videbaek L, Korup E, et al. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med. 2016;375(13):1221–30. https://doi.org/10.1056/NEJMoa1608029.

    Article  PubMed  Google Scholar 

  63. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2012;14(8):803–69. https://doi.org/10.1093/eurjhf/hfs105.

    Article  CAS  PubMed  Google Scholar 

  64. Duboc D, Meune C, Pierre B, Wahbi K, Eymard B, Toutain A, et al. Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years’ follow-up. Am Heart J. 2007;154(3):596–602. https://doi.org/10.1016/j.ahj.2007.05.014.

    Article  CAS  PubMed  Google Scholar 

  65. Mahon NG, Murphy RT, MacRae CA, Caforio AL, Elliott PM, McKenna WJ. Echocardiographic evaluation in asymptomatic relatives of patients with dilated cardiomyopathy reveals preclinical disease. Ann Intern Med. 2005;143(2):108–15.

    Article  PubMed  Google Scholar 

  66. Hershberger RE, Hedges DJ, Morales A. Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nat Rev Cardiol. 2013;10(9):531–47. https://doi.org/10.1038/nrcardio.2013.105.

    Article  CAS  PubMed  Google Scholar 

  67. Mestroni L, Brun F, Spezzacatene A, Sinagra G, Taylor MR. Genetic causes of dilated cardiomyopathy. Prog Pediatr Cardiol. 2014;37(1–2):13–8. https://doi.org/10.1016/j.ppedcard.2014.10.003.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Haas J, Frese KS, Peil B, Kloos W, Keller A, Nietsch R, et al. Atlas of the clinical genetics of human dilated cardiomyopathy. Eur Heart J. 2015;36(18):1123–35. https://doi.org/10.1093/eurheartj/ehu301.

    Article  CAS  PubMed  Google Scholar 

  69. Gerull B, Gramlich M, Atherton J, McNabb M, Trombitas K, Sasse-Klaassen S, et al. Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nat Genet. 2002;30(2):201–4. https://doi.org/10.1038/ng815.

    Article  CAS  PubMed  Google Scholar 

  70. Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012;366(7):619–28. https://doi.org/10.1056/NEJMoa1110186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, et al. Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease. Sci Transl Med. 2015;7(270):270ra276. https://doi.org/10.1126/scitranslmed.3010134.

    Article  CAS  Google Scholar 

  72. Fatkin D, MacRae C, Sasaki T, Wolff MR, Porcu M, Frenneaux M, et al. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med. 1999;341(23):1715–24. https://doi.org/10.1056/nejm199912023412302.

    Article  CAS  PubMed  Google Scholar 

  73. Kamisago M, Sharma SD, DePalma SR, Solomon S, Sharma P, McDonough B, et al. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med. 2000;343(23):1688–96. https://doi.org/10.1056/nejm200012073432304.

    Article  CAS  PubMed  Google Scholar 

  74. McNally EM, Puckelwartz MJ. Genetic variation in cardiomyopathy and cardiovascular disorders. Circ J. 2015;79(7):1409–15. https://doi.org/10.1253/circj.CJ-15-0536.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Akinrinade O, Alastalo TP, Koskenvuo JW. Relevance of truncating titin mutations in dilated cardiomyopathy. Clin Genet. 2016;90(1):49–54. https://doi.org/10.1111/cge.12741.

    Article  CAS  PubMed  Google Scholar 

  76. Brayson D, Shanahan CM. Current insights into LMNA cardiomyopathies: existing models and missing LINCs. Nucleus. 2017;8(1):17–33. https://doi.org/10.1080/19491034.2016.1260798.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Nikolova V, Leimena C, McMahon AC, Tan JC, Chandar S, Jogia D, et al. Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice. J Clin Invest. 2004;113(3):357–69. https://doi.org/10.1172/JCI19448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Bione S, Maestrini E, Rivella S, Mancini M, Regis S, Romeo G, Toniolo D. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat Genet. 1994;8(4):323–7. https://doi.org/10.1038/ng1294-323.

    Article  CAS  PubMed  Google Scholar 

  79. Arndt AK, Schafer S, Drenckhahn JD, Sabeh MK, Plovie ER, Caliebe A, et al. Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy. Am J Hum Genet. 2013;93(1):67–77. https://doi.org/10.1016/j.ajhg.2013.05.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kirk EP, Sunde M, Costa MW, Rankin SA, Wolstein O, Castro ML, et al. Mutations in cardiac T-box factor gene <em>TBX20</em> are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Am J Hum Genet. 2007;81(2):280–91. https://doi.org/10.1086/519530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Williams T, Hundertmark M, Nordbeck P, Voll S, Arias-Loza PA, Oppelt D, et al. Eya4 induces hypertrophy via regulation of p27kip1. Circ Cardiovasc Genet. 2015;8(6):752–64. https://doi.org/10.1161/circgenetics.115.001134.

    Article  CAS  PubMed  Google Scholar 

  82. Xu L, Zhao L, Yuan F, Jiang WF, Liu H, Li RG, et al. GATA6 loss-of-function mutations contribute to familial dilated cardiomyopathy. Int J Mol Med. 2014;34(5):1315–22. https://doi.org/10.3892/ijmm.2014.1896.

    Article  CAS  PubMed  Google Scholar 

  83. Yuan F, Qiu XB, Li RG, Qu XK, Wang J, Xu YJ, et al. A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias. Int J Mol Med. 2015;35(2):478–86. https://doi.org/10.3892/ijmm.2014.2029.

    Article  CAS  PubMed  Google Scholar 

  84. Guo W, Schafer S, Greaser ML, Radke MH, Liss M, Govindarajan T, et al. RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing. Nat Med. 2012;18(5):766–73. https://doi.org/10.1038/nm.2693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Maatz H, Jens M, Liss M, Schafer S, Heinig M, Kirchner M, et al. RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing. J Clin Invest. 2014;124(8):3419–30. https://doi.org/10.1172/jci74523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, et al. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science. 2003;299(5611):1410–3. https://doi.org/10.1126/science.1081578.

    Article  CAS  PubMed  Google Scholar 

  87. Abrol N, de Tombe PP, Robia SL. Acute inotropic and lusitropic effects of cardiomyopathic R9C mutation of phospholamban. J Biol Chem. 2015;290(11):7130–40. https://doi.org/10.1074/jbc.M114.630319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. McNair WP, Sinagra G, Taylor MRG, Di Lenarda A, Ferguson DA, Salcedo EE, et al. SCN5A mutations associate with arrhythmic dilated cardiomyopathy and commonly localize to the voltage-sensing mechanism. J Am Coll Cardiol. 2011;57(21):2160–8. https://doi.org/10.1016/j.jacc.2010.09.084.

    Article  PubMed  Google Scholar 

  89. Bienengraeber M, Olson TM, Selivanov VA, Kathmann EC, O'Cochlain F, Gao F, et al. ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating. Nat Genet. 2004;36(4):382–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Hershberger RE, Parks SB, Kushner JD, Li D, Ludwigsen S. Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy. Clin Transl Sci. 2008;1:21–6. https://doi.org/10.1111/j.1752-8062.2008.00017.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Geier C, Gehmlich K, Ehler E, Hassfeld S, Perrot A, Hayess K, et al. Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy. Hum Mol Genet. 2008;17(18):2753–65. https://doi.org/10.1093/hmg/ddn160.

    Article  CAS  PubMed  Google Scholar 

  92. Mohapatra B, Jimenez S, Lin JH, Bowles KR, Coveler KJ, Marx JG, et al. Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis. Mol Genet Metab. 2003;80(1-2):207–15.

    Article  CAS  PubMed  Google Scholar 

  93. Dalakas MC, Park KY, Semino-Mora C, Lee HS, Sivakumar K, Goldfarb LG. Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N Engl J Med. 2000;342(11):770–80. https://doi.org/10.1056/nejm200003163421104.

    Article  CAS  PubMed  Google Scholar 

  94. Arimura T, Ishikawa T, Nunoda S, Kawai S, Kimura A. Dilated cardiomyopathy-associated BAG3 mutations impair Z-disc assembly and enhance sensitivity to apoptosis in cardiomyocytes. Hum Mutat. 2011;32(12):1481–91. https://doi.org/10.1002/humu.21603.

    Article  CAS  PubMed  Google Scholar 

  95. Garcia-Pavia P, Syrris P, Salas C, Evans A, Mirelis JG, Cobo-Marcos M, et al. Desmosomal protein gene mutations in patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation: a clinicopathological study. Heart. 2011;97(21):1744–52. https://doi.org/10.1136/hrt.2011.227967.

    Article  CAS  PubMed  Google Scholar 

  96. Patel DM, Green KJ. Desmosomes in the heart: a review of clinical and mechanistic analyses. Cell Commun Adhes. 2014;21(3):109–28. https://doi.org/10.3109/15419061.2014.906533.

    Article  CAS  PubMed  Google Scholar 

  97. Behin A, Salort-Campana E, Wahbi K, Richard P, Carlier RY, Carlier P, et al. Myofibrillar myopathies: state of the art, present and future challenges. Rev Neurol (Paris). 2015;171(10):715–29. https://doi.org/10.1016/j.neurol.2015.06.002.

    Article  CAS  Google Scholar 

  98. Sommerville RB, Vincenti MG, Winborn K, Casey A, Stitziel NO, Connolly AM, Mann DL. Diagnosis and management of adult hereditary cardio-neuromuscular disorders: a model for the multidisciplinary care of complex genetic disorders. Trends Cardiovasc Med. 2017;27(1):51–8. https://doi.org/10.1016/j.tcm.2016.06.005.

    Article  PubMed  Google Scholar 

  99. Worman HJ, Bonne G. “Laminopathies”: a wide spectrum of human diseases. Exp Cell Res. 2007;313(10):2121–33. https://doi.org/10.1016/j.yexcr.2007.03.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kamdar F, Garry DJ. Dystrophin-deficient cardiomyopathy. J Am Coll Cardiol. 2016;67(21):2533–46. https://doi.org/10.1016/j.jacc.2016.02.081.

    Article  CAS  PubMed  Google Scholar 

  101. Pua CJ, Bhalshankar J, Miao K, Walsh R, John S, Lim SQ, et al. Development of a comprehensive sequencing assay for inherited cardiac condition genes. J Cardiovasc Transl Res. 2016;9(1):3–11. https://doi.org/10.1007/s12265-016-9673-5.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Akinrinade O, Ollila L, Vattulainen S, Tallila J, Gentile M, Salmenpera P, et al. Genetics and genotype-phenotype correlations in Finnish patients with dilated cardiomyopathy. Eur Heart J. 2015;36(34):2327–37. https://doi.org/10.1093/eurheartj/ehv253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Hershberger RE, Morales A. LMNA-related dilated cardiomyopathy. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews(R). Seattle (WA): University of Washington, Seattle; 1993.

    Google Scholar 

  104. Pasotti M, Klersy C, Pilotto A, Marziliano N, Rapezzi C, Serio A, et al. Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol. 2008;52(15):1250–60. https://doi.org/10.1016/j.jacc.2008.06.044.

    Article  PubMed  Google Scholar 

  105. van Rijsingen IAW, Arbustini E, Elliott PM, Mogensen J, Hermans-van Ast JF, van der Kooi AJ, et al. Risk factors for malignant ventricular arrhythmias in lamin A/C mutation carriers: a European Cohort Study. J Am Coll Cardiol. 2012;59(5):493–500. https://doi.org/10.1016/j.jacc.2011.08.078.

    Article  CAS  PubMed  Google Scholar 

  106. Franaszczyk M, Chmielewski P, Truszkowska G, Stawinski P, Michalak E, Rydzanicz M, et al. Titin truncating variants in dilated cardiomyopathy – prevalence and genotype-phenotype correlations. PLoS One. 2017;12(1):e0169007. https://doi.org/10.1371/journal.pone.0169007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Taylor MR, Fain PR, Sinagra G, Robinson ML, Robertson AD, Carniel E, et al. Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. J Am Coll Cardiol. 2003;41(5):771–80.

    Article  CAS  PubMed  Google Scholar 

  108. Roncarati R, Viviani Anselmi C, Krawitz P, Lattanzi G, von Kodolitsch Y, Perrot A, et al. Doubly heterozygous LMNA and TTN mutations revealed by exome sequencing in a severe form of dilated cardiomyopathy. Eur J Hum Genet. 2013;21(10):1105–11. https://doi.org/10.1038/ejhg.2013.16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of left ventricular myocardium. A study of eight cases. Circulation. 1990;82(2):507–13.

    Article  CAS  PubMed  Google Scholar 

  110. Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart. 2001;86(6):666–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Oechslin E, Jenni R. Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity? Eur Heart J. 2011;32(12):1446–56. https://doi.org/10.1093/eurheartj/ehq508.

    Article  PubMed  Google Scholar 

  112. Weir-McCall JR, Yeap PM, Papagiorcopulo C, Fitzgerald K, Gandy SJ, Lambert M, et al. Left ventricular noncompaction: anatomical phenotype or distinct cardiomyopathy? J Am Coll Cardiol. 2016;68(20):2157–65. https://doi.org/10.1016/j.jacc.2016.08.054.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Ichida F, Hamamichi Y, Miyawaki T, Ono Y, Kamiya T, Akagi T, et al. Clinical features of isolated noncompaction of the ventricular myocardium: long-term clinical course, hemodynamic properties, and genetic background. J Am Coll Cardiol. 1999;34(1):233–40.

    Article  CAS  PubMed  Google Scholar 

  114. Murphy RT, Thaman R, Blanes JG, Ward D, Sevdalis E, Papra E, et al. Natural history and familial characteristics of isolated left ventricular non-compaction. Eur Heart J. 2005;26(2):187–92. https://doi.org/10.1093/eurheartj/ehi025.

    Article  PubMed  Google Scholar 

  115. Oechslin EN, Attenhofer Jost CH, Rojas JR, Kaufmann PA, Jenni R. Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol. 2000;36(2):493–500.

    Article  CAS  PubMed  Google Scholar 

  116. Belanger AR, Miller MA, Donthireddi UR, Najovits AJ, Goldman ME. New classification scheme of left ventricular noncompaction and correlation with ventricular performance. Am J Cardiol. 2008;102(1):92–6. https://doi.org/10.1016/j.amjcard.2008.02.107.

    Article  PubMed  Google Scholar 

  117. Kohli SK, Pantazis AA, Shah JS, Adeyemi B, Jackson G, McKenna WJ, et al. Diagnosis of left-ventricular non-compaction in patients with left-ventricular systolic dysfunction: time for a reappraisal of diagnostic criteria? Eur Heart J. 2008;29(1):89–95. https://doi.org/10.1093/eurheartj/ehm481.

    Article  PubMed  Google Scholar 

  118. Zemrak F, Ahlman MA, Captur G, Mohiddin SA, Kawel-Boehm N, Prince MR, et al. The relationship of left ventricular trabeculation to ventricular function and structure over a 9.5-year follow-up: the MESA study. J Am Coll Cardiol. 2014;64(19):1971–80. https://doi.org/10.1016/j.jacc.2014.08.035.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Nugent AW, Daubeney PE, Chondros P, Carlin JB, Cheung M, Wilkinson LC, et al. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med. 2003;348(17):1639–46. https://doi.org/10.1056/NEJMoa021737.

    Article  PubMed  Google Scholar 

  120. Jefferies JL, Wilkinson JD, Sleeper LA, Colan SD, Lu M, Pahl E, et al. Cardiomyopathy phenotypes and outcomes for children with left ventricular myocardial noncompaction: results from the pediatric cardiomyopathy registry. J Card Fail. 2015;21(11):877–84. https://doi.org/10.1016/j.cardfail.2015.06.381.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Brescia ST, Rossano JW, Pignatelli R, Jefferies JL, Price JF, Decker JA, et al. Mortality and sudden death in pediatric left ventricular noncompaction in a tertiary referral center. Circulation. 2013;127(22):2202–8. https://doi.org/10.1161/CIRCULATIONAHA.113.002511.

    Article  PubMed  Google Scholar 

  122. Anderson RH, Jensen B, Mohun TJ, Petersen SE, Aung N, Zemrak F, et al. Key questions relating to left ventricular noncompaction cardiomyopathy: is the emperor still wearing any clothes? Can J Cardiol. 2017;33(6):747–57. https://doi.org/10.1016/j.cjca.2017.01.017.

    Article  PubMed  Google Scholar 

  123. Freedom RM, Yoo SJ, Perrin D, Taylor G, Petersen S, Anderson RH. The morphological spectrum of ventricular noncompaction. Cardiol Young. 2005;15(4):345–64. https://doi.org/10.1017/S1047951105000752.

    Article  PubMed  Google Scholar 

  124. Kodo K, Ong SG, Jahanbani F, Termglinchan V, Hirono K, InanlooRahatloo K, et al. iPSC-derived cardiomyocytes reveal abnormal TGF-beta signalling in left ventricular non-compaction cardiomyopathy. Nat Cell Biol. 2016;18(10):1031–42. https://doi.org/10.1038/ncb3411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Grego-Bessa J, Luna-Zurita L, del Monte G, Bolos V, Melgar P, Arandilla A, et al. Notch signaling is essential for ventricular chamber development. Dev Cell. 2007;12(3):415–29. https://doi.org/10.1016/j.devcel.2006.12.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Sasse-Klaassen S, Gerull B, Oechslin E, Jenni R, Thierfelder L. Isolated noncompaction of the left ventricular myocardium in the adult is an autosomal dominant disorder in the majority of patients. Am J Med Genet A. 2003;119A(2):162–7. https://doi.org/10.1002/ajmg.a.20075.

    Article  PubMed  Google Scholar 

  127. Probst S, Oechslin E, Schuler P, Greutmann M, Boye P, Knirsch W, et al. Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype. Circ Cardiovasc Genet. 2011;4(4):367–74. https://doi.org/10.1161/CIRCGENETICS.110.959270.

    Article  CAS  PubMed  Google Scholar 

  128. Budde BS, Binner P, Waldmuller S, Hohne W, Blankenfeldt W, Hassfeld S, et al. Noncompaction of the ventricular myocardium is associated with a de novo mutation in the beta-myosin heavy chain gene. PLoS One. 2007;2(12):e1362. https://doi.org/10.1371/journal.pone.0001362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Hoedemaekers YM, Caliskan K, Michels M, Frohn-Mulder I, van der Smagt JJ, Phefferkorn JE, et al. The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy. Circ Cardiovasc Genet. 2010;3(3):232–9. https://doi.org/10.1161/CIRCGENETICS.109.903898.

    Article  PubMed  Google Scholar 

  130. Klaassen S, Probst S, Oechslin E, Gerull B, Krings G, Schuler P, et al. Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation. 2008;117(22):2893–901. https://doi.org/10.1161/CIRCULATIONAHA.107.746164.

    Article  CAS  PubMed  Google Scholar 

  131. Postma AV, van Engelen K, van de Meerakker J, Rahman T, Probst S, Baars MJ, et al. Mutations in the sarcomere gene MYH7 in Ebstein anomaly. Circ Cardiovasc Genet. 2011;4(1):43–50. https://doi.org/10.1161/CIRCGENETICS.110.957985.

    Article  CAS  PubMed  Google Scholar 

  132. Wessels MW, Herkert JC, Frohn-Mulder IM, Dalinghaus M, van den Wijngaard A, de Krijger RR, et al. Compound heterozygous or homozygous truncating MYBPC3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects. Eur J Hum Genet. 2015;23(7):922–8. https://doi.org/10.1038/ejhg.2014.211.

    Article  CAS  PubMed  Google Scholar 

  133. Monserrat L, Hermida-Prieto M, Fernandez X, Rodriguez I, Dumont C, Cazon L, et al. Mutation in the alpha-cardiac actin gene associated with apical hypertrophic cardiomyopathy, left ventricular non-compaction, and septal defects. Eur Heart J. 2007;28(16):1953–61. https://doi.org/10.1093/eurheartj/ehm239.

    Article  CAS  PubMed  Google Scholar 

  134. Hastings R, de Villiers CP, Hooper C, Ormondroyd L, Pagnamenta A, Lise S, et al. Combination of whole genome sequencing, linkage, and functional studies implicates a missense mutation in titin as a cause of autosomal dominant cardiomyopathy with features of left ventricular noncompaction. Circ Cardiovasc Genet. 2016;9(5):426–35. https://doi.org/10.1161/CIRCGENETICS.116.001431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Bleyl SB, Mumford BR, Thompson V, Carey JC, Pysher TJ, Chin TK, Ward K. Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome. Am J Hum Genet. 1997;61(4):868–72. https://doi.org/10.1086/514879.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Vatta M, Mohapatra B, Jimenez S, Sanchez X, Faulkner G, Perles Z, et al. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. J Am Coll Cardiol. 2003;42(11):2014–27.

    Article  CAS  PubMed  Google Scholar 

  137. Bagnall RD, Molloy LK, Kalman JM, Semsarian C. Exome sequencing identifies a mutation in the ACTN2 gene in a family with idiopathic ventricular fibrillation, left ventricular noncompaction, and sudden death. BMC Med Genet. 2014;15:99. https://doi.org/10.1186/s12881-014-0099-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Milano A, Vermeer AM, Lodder EM, Barc J, Verkerk AO, Postma AV, et al. HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy. J Am Coll Cardiol. 2014;64(8):745–56. https://doi.org/10.1016/j.jacc.2014.05.045.

    Article  CAS  PubMed  Google Scholar 

  139. Schweizer PA, Schroter J, Greiner S, Haas J, Yampolsky P, Mereles D, et al. The symptom complex of familial sinus node dysfunction and myocardial noncompaction is associated with mutations in the HCN4 channel. J Am Coll Cardiol. 2014;64(8):757–67. https://doi.org/10.1016/j.jacc.2014.06.1155.

    Article  CAS  PubMed  Google Scholar 

  140. Shan L, Makita N, Xing Y, Watanabe S, Futatani T, Ye F, et al. SCN5A variants in Japanese patients with left ventricular noncompaction and arrhythmia. Mol Genet Metab. 2008;93(4):468–74.

    Article  CAS  PubMed  Google Scholar 

  141. Hermida-Prieto M, Monserrat L, Castro-Beiras A, Laredo R, Soler R, Peteiro J, et al. Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations. Am J Cardiol. 2004;94(1):50–4. https://doi.org/10.1016/j.amjcard.2004.03.029.

    Article  PubMed  Google Scholar 

  142. Luxan G, Casanova JC, Martinez-Poveda B, Prados B, D'Amato G, MacGrogan D, et al. Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy. Nat Med. 2013;19(2):193–201. https://doi.org/10.1038/nm.3046.

    Article  CAS  PubMed  Google Scholar 

  143. Hoedemaekers YM, Klaassen S. Left ventricular noncompaction. In: Baars HF, Doevendans PAFM, Houweling A, Tintelen JP, editors. Clinical cardiogenetics. Berlin: Springer; 2016. p. 113–35. https://doi.org/10.1007/978-3-319-44203-7.

    Chapter  Google Scholar 

  144. Ichida F, Tsubata S, Bowles KR, Haneda N, Uese K, Miyawaki T, et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation. 2001;103(9):1256–63.

    Article  CAS  PubMed  Google Scholar 

  145. Williams T, Machann W, Kuhler L, Hamm H, Muller-Hocker J, Zimmer M, et al. Novel desmoplakin mutation: juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma. Clin Res Cardiol. 2011;100(12):1087–93. https://doi.org/10.1007/s00392-011-0345-9.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Stahli BE, Gebhard C, Biaggi P, Klaassen S, Valsangiacomo Buechel E, Attenhofer Jost CH, et al. Left ventricular non-compaction: prevalence in congenital heart disease. Int J Cardiol. 2013;167(6):2477–81. https://doi.org/10.1016/j.ijcard.2012.05.095.

    Article  PubMed  Google Scholar 

  147. Ouyang P, Saarel E, Bai Y, Luo C, Lv Q, Xu Y, et al. A de novo mutation in NKX2.5 associated with atrial septal defects, ventricular noncompaction, syncope and sudden death. Clin Chim Acta. 2011;412(1-2):170–5. https://doi.org/10.1016/j.cca.2010.09.035.

    Article  CAS  PubMed  Google Scholar 

  148. Finsterer J, Stollberger C, Towbin JA. Left ventricular noncompaction cardiomyopathy: cardiac, neuromuscular, and genetic factors. Nat Rev Cardiol. 2017;14(4):224–37. https://doi.org/10.1038/nrcardio.2016.207.

    Article  PubMed  Google Scholar 

  149. Scaglia F, Towbin JA, Craigen WJ, Belmont JW, Smith EO, Neish SR, et al. Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics. 2004;114(4):925–31. https://doi.org/10.1542/peds.2004-0718.

    Article  PubMed  Google Scholar 

  150. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation. 2010;121(13):1533–41. https://doi.org/10.1161/CIRCULATIONAHA.108.840827.

    Article  PubMed  PubMed Central  Google Scholar 

  151. Lancisi GM. De motu cordis et aneurysmatibus opus postumum. 1740.

    Google Scholar 

  152. Marcus FI, Fontaine GH, Guiraudon G, Frank R, Laurenceau JL, Malergue C, Grosgogeat Y. Right ventricular dysplasia: a report of 24 adult cases. Circulation. 1982;65(2):384–98.

    Article  CAS  PubMed  Google Scholar 

  153. Romero J, Mejia-Lopez E, Manrique C, Lucariello R. Arrhythmogenic right ventricular cardiomyopathy (ARVC/D): a systematic literature review. Clin Med Insights Cardiol. 2013;7:97–114. https://doi.org/10.4137/CMC.S10940.

    Article  PubMed  PubMed Central  Google Scholar 

  154. Bhonsale A, Te Riele A, Sawant AC, Groeneweg JA, James CA, Murray B, et al. Cardiac phenotype and long-term prognosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia patients with late presentation. Heart Rhythm. 2017;14(6):883–91. https://doi.org/10.1016/j.hrthm.2017.02.013.

    Article  PubMed  Google Scholar 

  155. McKenna WJ, Thiene G, Nava A, Fontaliran F, Blomstrom-Lundqvist C, Fontaine G, Camerini F. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology. Br Heart J. 1994;71(3):215–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. van der Zwaag PA, van Rijsingen IA, Asimaki A, Jongbloed JD, van Veldhuisen DJ, Wiesfeld AC, et al. Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy. Eur J Heart Fail. 2012;14(11):1199–207. https://doi.org/10.1093/eurjhf/hfs119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Xu T, Yang Z, Vatta M, Rampazzo A, Beffagna G, Pilichou K, et al. Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy. J Am Coll Cardiol. 2010;55(6):587–97. https://doi.org/10.1016/j.jacc.2009.11.020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, et al. De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy. Hum Mol Genet. 2010;19(23):4595–607. https://doi.org/10.1093/hmg/ddq387.

    Article  CAS  PubMed  Google Scholar 

  159. Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, Rossi V, et al. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2002;71(5):1200–6. https://doi.org/10.1086/344208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Heuser A, Plovie ER, Ellinor PT, Grossmann KS, Shin JT, Wichter T, et al. Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet. 2006;79(6):1081–8. https://doi.org/10.1086/509044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Syrris P, Ward D, Evans A, Asimaki A, Gandjbakhch E, Sen-Chowdhry S, McKenna WJ. Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am J Hum Genet. 2006;79(5):978–84. https://doi.org/10.1086/509122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Pilichou K, Nava A, Basso C, Beffagna G, Bauce B, Lorenzon A, et al. Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy. Circulation. 2006;113(9):1171–9. https://doi.org/10.1161/CIRCULATIONAHA.105.583674.

    Article  CAS  PubMed  Google Scholar 

  163. Vermij SH, Abriel H, van Veen TA. Refining the molecular organization of the cardiac intercalated disc. Cardiovasc Res. 2017;113(3):259–75. https://doi.org/10.1093/cvr/cvw259.

    Article  CAS  PubMed  Google Scholar 

  164. Mayosi BM, Fish M, Shaboodien G, Mastantuono E, Kraus S, Wieland T, et al. Identification of cadherin 2 (CDH2) mutations in arrhythmogenic right ventricular cardiomyopathy. Circ Cardiovasc Genet. 2017;10(2):e001605. https://doi.org/10.1161/CIRCGENETICS.116.001605.

    Article  CAS  PubMed  Google Scholar 

  165. van Hengel J, Calore M, Bauce B, Dazzo E, Mazzotti E, De Bortoli M, et al. Mutations in the area composita protein alphaT-catenin are associated with arrhythmogenic right ventricular cardiomyopathy. Eur Heart J. 2013;34(3):201–10. https://doi.org/10.1093/eurheartj/ehs373.

    Article  CAS  PubMed  Google Scholar 

  166. Fressart V, Duthoit G, Donal E, Probst V, Deharo JC, Chevalier P, et al. Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice. Europace. 2010;12(6):861–8. https://doi.org/10.1093/europace/euq104.

    Article  PubMed  Google Scholar 

  167. Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001;10(3):189–94.

    Article  CAS  PubMed  Google Scholar 

  168. Beffagna G, Occhi G, Nava A, Vitiello L, Ditadi A, Basso C, et al. Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res. 2005;65(2):366–73. https://doi.org/10.1016/j.cardiores.2004.10.005.

    Article  CAS  PubMed  Google Scholar 

  169. Merner ND, Hodgkinson KA, Haywood AF, Connors S, French VM, Drenckhahn JD, et al. Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene. Am J Hum Genet. 2008;82(4):809–21. https://doi.org/10.1016/j.ajhg.2008.01.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Erkapic D, Neumann T, Schmitt J, Sperzel J, Berkowitsch A, Kuniss M, et al. Electrical storm in a patient with arrhythmogenic right ventricular cardiomyopathy and SCN5A mutation. Europace. 2008;10(7):884–7. https://doi.org/10.1093/europace/eun065.

    Article  PubMed  Google Scholar 

  171. Taylor M, Graw S, Sinagra G, Barnes C, Slavov D, Brun F, et al. Genetic variation in titin in arrhythmogenic right ventricular cardiomyopathy-overlap syndromes. Circulation. 2011;124(8):876–85. https://doi.org/10.1161/CIRCULATIONAHA.110.005405.

    Article  PubMed  PubMed Central  Google Scholar 

  172. Quarta G, Syrris P, Ashworth M, Jenkins S, Zuborne Alapi K, Morgan J, et al. Mutations in the Lamin A/C gene mimic arrhythmogenic right ventricular cardiomyopathy. Eur Heart J. 2012;33(9):1128–36. https://doi.org/10.1093/eurheartj/ehr451.

    Article  CAS  PubMed  Google Scholar 

  173. Lopez-Ayala JM, Ortiz-Genga M, Gomez-Milanes I, Lopez-Cuenca D, Ruiz-Espejo F, Sanchez-Munoz JJ, et al. A mutation in the Z-line Cypher/ZASP protein is associated with arrhythmogenic right ventricular cardiomyopathy. Clin Genet. 2015;88(2):172–6. https://doi.org/10.1111/cge.12458.

    Article  CAS  PubMed  Google Scholar 

  174. Xiong Q, Cao Q, Zhou Q, Xie J, Shen Y, Wan R, et al. Arrhythmogenic cardiomyopathy in a patient with a rare loss-of-function KCNQ1 mutation. J Am Heart Assoc. 2015;4(1):e001526. https://doi.org/10.1161/JAHA.114.001526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Protonotarios N, Tsatsopoulou A. Naxos disease: cardiocutaneous syndrome due to cell adhesion defect. Orphanet J Rare Dis. 2006;1:4. https://doi.org/10.1186/1750-1172-1-4.

    Article  PubMed  PubMed Central  Google Scholar 

  176. Brogna S, Wen J. Nonsense-mediated mRNA decay (NMD) mechanisms. Nat Struct Mol Biol. 2009;16(2):107–13. https://doi.org/10.1038/nsmb.1550.

    Article  CAS  PubMed  Google Scholar 

  177. Zhang Z, Stroud MJ, Zhang J, Fang X, Ouyang K, Kimura K, et al. Normalization of Naxos plakoglobin levels restores cardiac function in mice. J Clin Invest. 2015;125(4):1708–12. https://doi.org/10.1172/JCI80335.

    Article  PubMed  PubMed Central  Google Scholar 

  178. Norgett EE, Hatsell SJ, Carvajal-Huerta L, Cabezas JC, Common J, Purkis PE, et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet. 2000;9(18):2761–6.

    Article  CAS  PubMed  Google Scholar 

  179. Green KJ, Stappenbeck TS, Parry DA, Virata ML. Structure of desmoplakin and its association with intermediate filaments. J Dermatol. 1992;19(11):765–9.

    Article  CAS  PubMed  Google Scholar 

  180. Chen X, Bonne S, Hatzfeld M, van Roy F, Green KJ. Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta-catenin signaling. J Biol Chem. 2002;277(12):10512–22. https://doi.org/10.1074/jbc.M108765200.

    Article  CAS  PubMed  Google Scholar 

  181. Nekrasova OE, Amargo EV, Smith WO, Chen J, Kreitzer GE, Green KJ. Desmosomal cadherins utilize distinct kinesins for assembly into desmosomes. J Cell Biol. 2011;195(7):1185–203. https://doi.org/10.1083/jcb.201106057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Kirchner F, Schuetz A, Boldt LH, Martens K, Dittmar G, Haverkamp W, et al. Molecular insights into arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 missense mutations. Circ Cardiovasc Genet. 2012;5(4):400–11. https://doi.org/10.1161/CIRCGENETICS.111.961854.

    Article  CAS  PubMed  Google Scholar 

  183. Harrison OJ, Brasch J, Lasso G, Katsamba PS, Ahlsen G, Honig B, Shapiro L. Structural basis of adhesive binding by desmocollins and desmogleins. Proc Natl Acad Sci USA. 2016;113(26):7160–5. https://doi.org/10.1073/pnas.1606272113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Gerull B, Kirchner F, Chong JX, Tagoe J, Chandrasekharan K, Strohm O, et al. Homozygous founder mutation in desmocollin-2 (DSC2) causes arrhythmogenic cardiomyopathy in the Hutterite population. Circ Cardiovasc Genet. 2013;6(4):327–36. https://doi.org/10.1161/CIRCGENETICS.113.000097.

    Article  CAS  PubMed  Google Scholar 

  185. Simpson MA, Mansour S, Ahnood D, Kalidas K, Patton MA, McKenna WJ, et al. Homozygous mutation of desmocollin-2 in arrhythmogenic right ventricular cardiomyopathy with mild palmoplantar keratoderma and woolly hair. Cardiology. 2009;113(1):28–34. https://doi.org/10.1159/000165696.

    Article  CAS  PubMed  Google Scholar 

  186. Wong JA, Duff HJ, Yuen T, Kolman L, Exner DV, Weeks SG, Gerull B. Phenotypic analysis of arrhythmogenic cardiomyopathy in the Hutterite population: role of electrocardiogram in identifying high-risk desmocollin-2 carriers. J Am Heart Assoc. 2014;3(6):e001407. https://doi.org/10.1161/JAHA.114.001407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. van Tintelen JP, Van Gelder IC, Asimaki A, Suurmeijer AJ, Wiesfeld AC, Jongbloed JD, et al. Severe cardiac phenotype with right ventricular predominance in a large cohort of patients with a single missense mutation in the DES gene. Heart Rhythm. 2009;6(11):1574–83. https://doi.org/10.1016/j.hrthm.2009.07.041.

    Article  PubMed  Google Scholar 

  188. Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, et al. Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants. J Biol Chem. 2012;287(19):16047–57. https://doi.org/10.1074/jbc.M111.313841.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Turkowski KL, Tester DJ, Bos JM, Haugaa KH, Ackerman MJ. Whole exome sequencing with genomic triangulation implicates CDH2-encoded N-cadherin as a novel pathogenic substrate for arrhythmogenic cardiomyopathy. Congenit Heart Dis. 2017;12(2):226–35. https://doi.org/10.1111/chd.12462.

    Article  PubMed  Google Scholar 

  190. Bers DM, Perez-Reyes E. Ca channels in cardiac myocytes: structure and function in Ca influx and intracellular Ca release. Cardiovasc Res. 1999;42(2):339–60.

    Article  CAS  PubMed  Google Scholar 

  191. Kranias EG, Bers DM. Calcium and cardiomyopathies. Subcell Biochem. 2007;45:523–37.

    Article  CAS  PubMed  Google Scholar 

  192. Ma Y, Zou H, Zhu XX, Pang J, Xu Q, Jin QY, et al. Transforming growth factor beta: a potential biomarker and therapeutic target of ventricular remodeling. Oncotarget. 2017;8(32):53780–90. https://doi.org/10.18632/oncotarget.17255.

    Article  PubMed  PubMed Central  Google Scholar 

  193. Milting H, Klauke B, Christensen AH, Musebeck J, Walhorn V, Grannemann S, et al. The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus. Eur Heart J. 2015;36(14):872–81. https://doi.org/10.1093/eurheartj/ehu077.

    Article  CAS  PubMed  Google Scholar 

  194. Bengtsson L, Otto H. LUMA interacts with emerin and influences its distribution at the inner nuclear membrane. J Cell Sci. 2008;121(Pt 4):536–48. https://doi.org/10.1242/jcs.019281.

    Article  CAS  PubMed  Google Scholar 

  195. Garcia MJ. Constrictive pericarditis versus restrictive cardiomyopathy? J Am Coll Cardiol. 2016;67(17):2061–76. https://doi.org/10.1016/j.jacc.2016.01.076.

    Article  PubMed  Google Scholar 

  196. Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl J Med. 1997;336(4):267–76. https://doi.org/10.1056/NEJM199701233360407.

    Article  CAS  PubMed  Google Scholar 

  197. Schulz V, Hendig D, Szliska C, Gotting C, Kleesiek K. Novel mutations in the ABCC6 gene of German patients with pseudoxanthoma elasticum. Hum Biol. 2005;77(3):367–84.

    Article  PubMed  Google Scholar 

  198. Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012;126(10):1286–300. https://doi.org/10.1161/CIRCULATIONAHA.111.078915.

    Article  PubMed  PubMed Central  Google Scholar 

  199. Kostareva A, Kiselev A, Gudkova A, Frishman G, Ruepp A, Frishman D, et al. Genetic spectrum of idiopathic restrictive cardiomyopathy uncovered by next-generation sequencing. PLoS One. 2016;11(9):e0163362. https://doi.org/10.1371/journal.pone.0163362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Mogensen J, Kubo T, Duque M, Uribe W, Shaw A, Murphy R, et al. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J Clin Invest. 2003;111(2):209–16. https://doi.org/10.1172/JCI16336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Filatov VL, Katrukha AG, Bulargina TV, Gusev NB. Troponin: structure, properties, and mechanism of functioning. Biochemistry (Mosc). 1999;64(9):969–85.

    CAS  Google Scholar 

  202. Peddy SB, Vricella LA, Crosson JE, Oswald GL, Cohn RD, Cameron DE, et al. Infantile restrictive cardiomyopathy resulting from a mutation in the cardiac troponin T gene. Pediatrics. 2006;117(5):1830–3. https://doi.org/10.1542/peds.2005-2301.

    Article  PubMed  Google Scholar 

  203. Ploski R, Rydzanicz M, Ksiazczyk TM, Franaszczyk M, Pollak A, Kosinska J, et al. Evidence for troponin C (TNNC1) as a gene for autosomal recessive restrictive cardiomyopathy with fatal outcome in infancy. Am J Med Genet A. 2016;170(12):3241–8. https://doi.org/10.1002/ajmg.a.37860.

    Article  CAS  PubMed  Google Scholar 

  204. Marques MA, de Oliveira GA. Cardiac troponin and tropomyosin: structural and cellular perspectives to unveil the hypertrophic cardiomyopathy phenotype. Front Physiol. 2016;7:429. https://doi.org/10.3389/fphys.2016.00429.

    Article  PubMed  PubMed Central  Google Scholar 

  205. Karam S, Raboisson MJ, Ducreux C, Chalabreysse L, Millat G, Bozio A, Bouvagnet P. A de novo mutation of the beta cardiac myosin heavy chain gene in an infantile restrictive cardiomyopathy. Congenit Heart Dis. 2008;3(2):138–43. https://doi.org/10.1111/j.1747-0803.2008.00165.x.

    Article  PubMed  Google Scholar 

  206. Kaski JP, Syrris P, Burch M, Tome-Esteban MT, Fenton M, Christiansen M, et al. Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes. Heart. 2008;94(11):1478–84. https://doi.org/10.1136/hrt.2007.134684.

    Article  CAS  PubMed  Google Scholar 

  207. Wu W, Lu CX, Wang YN, Liu F, Chen W, Liu YT, et al. Novel phenotype-genotype correlations of restrictive cardiomyopathy with myosin-binding protein C (MYBPC3) gene mutations tested by next-generation sequencing. J Am Heart Assoc. 2015;4(7):e001879. https://doi.org/10.1161/JAHA.115.001879.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Peled Y, Gramlich M, Yoskovitz G, Feinberg MS, Afek A, Polak-Charcon S, et al. Titin mutation in familial restrictive cardiomyopathy. Int J Cardiol. 2014;171(1):24–30. https://doi.org/10.1016/j.ijcard.2013.11.037.

    Article  PubMed  Google Scholar 

  209. Purevjav E, Arimura T, Augustin S, Huby AC, Takagi K, Nunoda S, et al. Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations. Hum Mol Genet. 2012;21(9):2039–53. https://doi.org/10.1093/hmg/dds022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Bang ML, Mudry RE, McElhinny AS, Trombitas K, Geach AJ, Yamasaki R, et al. Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. J Cell Biol. 2001;153(2):413–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Arbustini E, Pasotti M, Pilotto A, Pellegrini C, Grasso M, Previtali S, et al. Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects. Eur J Heart Fail. 2006;8(5):477–83. https://doi.org/10.1016/j.ejheart.2005.11.003.

    Article  CAS  PubMed  Google Scholar 

  212. Brodehl A, Ferrier RA, Hamilton SJ, Greenway SC, Brundler MA, Yu W, et al. Mutations in FLNC are associated with familial restrictive cardiomyopathy. Hum Mutat. 2016;37(3):269–79. https://doi.org/10.1002/humu.22942.

    Article  CAS  PubMed  Google Scholar 

  213. Brodehl A, Gaertner-Rommel A, Klauke B, Grewe SA, Schirmer I, Peterschroder A, et al. The novel alphaB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy. Hum Mutat. 2017;38(8):947–52. https://doi.org/10.1002/humu.23248.

    Article  CAS  PubMed  Google Scholar 

  214. Goldfarb LG, Dalakas MC. Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle disease. J Clin Invest. 2009;119(7):1806–13. https://doi.org/10.1172/JCI38027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Jahed Z, Shams H, Mehrbod M, Mofrad MR. Mechanotransduction pathways linking the extracellular matrix to the nucleus. Int Rev Cell Mol Biol. 2014;310:171–220. https://doi.org/10.1016/B978-0-12-800180-6.00005-0.

    Article  CAS  PubMed  Google Scholar 

  216. Olive M, Kley RA, Goldfarb LG. Myofibrillar myopathies: new developments. Curr Opin Neurol. 2013;26(5):527–35. https://doi.org/10.1097/WCO.0b013e328364d6b1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine I, Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany

    Brenda Gerull

  2. Experimental and Clinical Research Center (ECRC), Max-Delbrück-Center for Molecular Medicine, Charité University Medicine Berlin, Berlin, Germany

    Sabine Klaassen

  3. Heart and Diabetes Centre NRW, Erich and Hanna Klessmann Institute, University Hospital of the Ruhr-University Bochum, Bad Oeynhausen, Germany

    Andreas Brodehl

Authors
  1. Brenda Gerull
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sabine Klaassen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andreas Brodehl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brenda Gerull .

Editor information

Editors and Affiliations

  1. IIEG, University of Lubeck, Lübeck, Germany

    Jeanette Erdmann

  2. I Medical Dept (Cardiology), Klinikum Rechts der Isar of the Technical University Munich, München, Bayern, Germany

    Alessandra Moretti

Ethics declarations

Conflict of Interest

Brenda Gerull declares that she has no conflict of interest. Sabine Klaassen declares that she has no conflict of interest. Andreas Brodehl declares that he has no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gerull, B., Klaassen, S., Brodehl, A. (2019). The Genetic Landscape of Cardiomyopathies. In: Erdmann, J., Moretti, A. (eds) Genetic Causes of Cardiac Disease. Cardiac and Vascular Biology, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-030-27371-2_2

Download citation

Publish with us

Policies and ethics

Search

Navigation