Heart Rhythm
Volume 6, Issue 11 , Pages 1574-1583 , November 2009

Severe cardiac phenotype with right ventricular predominance in a large cohort of patients with a single missense mutation in the DES gene

  • J. Peter van Tintelen, MD, PhD

      Affiliations

    • Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    • Corresponding Author InformationAddress reprint requests and correspondence: Dr. J. Peter van Tintelen, Department of Genetics, University Medical Center Groningen, University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands
  • ,
  • Isabelle C. Van Gelder, MD, PhD

      Affiliations

    • Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    • Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
  • ,
  • Angeliki Asimaki, PhD

      Affiliations

    • Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • ,
  • Albert J.H. Suurmeijer, MD, PhD

      Affiliations

    • Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • ,
  • Ans C.P. Wiesfeld, MD, PhD

      Affiliations

    • Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • ,
  • Jan D.H. Jongbloed, PhD

      Affiliations

    • Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • ,
  • Arthur van den Wijngaard, PhD

      Affiliations

    • Department of Clinical Genetics, University Hospital Maastricht, Maastricht, The Netherlands
  • ,
  • Jan B.M. Kuks, MD, PhD

      Affiliations

    • Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • ,
  • Karin Y. van Spaendonck-Zwarts, MD

      Affiliations

    • Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • ,
  • Nicolette Notermans, MD, PhD

      Affiliations

    • Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
  • ,
  • Ludolf Boven, BS

      Affiliations

    • Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • ,
  • Freek van den Heuvel, MD, PhD

      Affiliations

    • Department of Pediatric Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • ,
  • Hermine E. Veenstra-Knol, MD

      Affiliations

    • Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • ,
  • Jeffrey E. Saffitz, MD, PhD

      Affiliations

    • Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • ,
  • Robert M.W. Hofstra, PhD

      Affiliations

    • Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • ,
  • Maarten P. van den Berg, MD, PhD

      Affiliations

    • Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Received 6 March 2009 ,Accepted 23 July 2009.

References 

  1. Bär H, Strelkov SV, Sjöberg G, et al. The biology of desmin filaments: how do mutations affect their structure, assembly, and organisation?. J Struct Biol. 2004;148:137–152
  2. Goldfarb LG, Park KY, Cervenáková L, et al. Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet. 1998;19:402–403
  3. Dalakas MC, Park KY, Semino-Mora C, et al. Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N Engl J Med. 2000;342:770–780
  4. Goudeau B, Dagvadorj A, Rodrigues-Lima F, et al. Structural and functional analysis of a new desmin variant causing desmin-related myopathy. Hum Mutat. 2001;18:388–396
  5. Li M, Dalakas MC. Abnormal desmin protein in myofibrillar myopathies caused by desmin gene mutations. Ann Neurol. 2001;49:532–536
  6. Dagvadorj A, Goudeau B, Hilton-Jones D, et al. Respiratory insufficiency in desminopathy patients caused by introduction of proline residues in desmin c-terminal alpha-helical segment. Muscle Nerve. 2003;27:669–675
  7. Dalakas MC, Dagvadorj A, Goudeau B, et al. Progressive skeletal myopathy, a phenotypic variant of desmin myopathy associated with desmin mutations. Neuromuscul Disord. 2003;13:252–258
  8. Kaminska A, Strelkov SV, Goudeau B, et al. Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy. Hum Genet. 2004;114:306–313
  9. Olivé M, Goldfarb L, Moreno D, et al. Desmin-related myopathy: clinical, electrophysiological, radiological, neuropathological and genetic studies. J Neurol Sci. 2004;219:125–137
  10. Arbustini E, Pasotti M, Pilotto A, et al. Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects. Eur J Heart Fail. 2006;8:477–483
  11. Kostera-Pruszczyk A, Pruszczyk P, Kaminńska A, et al. Diversity of cardiomyopathy phenotypes caused by mutations in desmin. Int J Cardiol. 2008;131:146–147
  12. Bergman JE, Veenstra-Knol HE, van Essen AJ, et al. Two related Dutch families with a clinically variable presentation of cardioskeletal myopathy caused by a novel S13F mutation in the desmin gene. Eur J Med Genet. 2007;50:355–366
  13. Gardin JM, Adams DB, Douglas PS, et al. American Society of Echocardiography Recommendations for a standardized report for adult transthoracic echocardiography: a report from the American Society of Echocardiography's Nomenclature and Standards Committee and Task Force for a Standardized Echocardiography Report. J Am Soc Echocardiogr. 2002;15:275–290
  14. Mestroni L, Maisch B, McKenna WJ, et al. Guidelines for the study of familial dilated cardiomyopathies (Collaborative Research Group of the European Human and Capital Mobility Project on Familial Dilated Cardiomyopathy). Eur Heart J. 1999;20:93–102
  15. McKenna WJ, Thiene G, Nava A, et al. 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;71:215–218
  16. Wu Y, Hayes VM, Osinga J, et al. Improvement of fragment and primer selection for mutation detection by denaturing gradient gel electrophoresis. Nucleic Acids Res. 1998;26:5432–5440
  17. Hayes VM, Wu Y, Osinga J, et al. Improvements in gel composition and electrophoretic conditions for broad-range mutation analysis by denaturing gradient gel electrophoresis. Nucleic Acids Res. 1999;27:e29
  18. van Tintelen JP, Hofstra RM, Katerberg H, et al. High yield of LMNA mutations in patients with dilated cardiomyopathy and/or conduction disease referred to cardiogenetics outpatient clinics. Am Heart J. 2007;154:1130–1139
  19. Machado PM, Brandão RD, Cavaco BM, et al. Screening for a BRCA2 rearrangement in high-risk breast/ovarian cancer families: evidence for a founder effect and analysis of the associated phenotypes. J Clin Oncol. 2007;25:2027–2034
  20. Saffitz JE, Green KG, Kraft WJ, et al. Effects of diminished expression of connexin43 on gap junction number and size in ventricular myocardium. Am J Physiol Heart Circ Physiol. 2000;278:H1662–H1670
  21. Van Gelder IC, Boriani G, Ernst S, et al. EHRA Education Committee Case of the month by the EHRA Education committee: exercise-related arrhythmias. Europace. 2008;10:235–237
  22. van den Berg MP, Nagelkerke D, Brouwer RM, et al. Feasibility of pacemaker therapy after dynamic cardiomyoplasty. Pacing Clin Electrophysiol. 1999;22:1543–1546
  23. Olivé M, van Leeuwen FW, Janué A, et al. Expression of mutant ubiquitin (UBB+1) and p62 in myotilinopathies and desminopathies. Neuropathol Appl Neurobiol. 2008;34:76–87
  24. Selcen D, Ohno K, Engel AG. Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain. 2004;127:439–451
  25. Taylor MR, Slavov D, Ku L, et al. Familial Cardiomyopathy Registry; BEST (Beta-Blocker Evaluation of Survival Trial) DNA Bank Prevalence of desmin mutations in dilated cardiomyopathy. Circulation. 2007;115:1244–1251
  26. Raats JM, Pieper FR, Vree Egberts WT, et al. Assembly of amino-terminally deleted desmin in vimentin-free cells. J Cell Biol. 1990;111:1971–1985
  27. Lapouge K, Fontao L, Champliaud MF, et al. New insights into the molecular basis of desmoplakin- and desmin-related cardiomyopathies. J Cell Sci. 2006;119:4974–4985
  28. Pica EC, Kathirvel P, Pramono ZA, et al. Characterization of a novel S13F desmin mutation associated with desmin myopathy and heart block in a Chinese family. Neuromuscul Disord. 2008;18:178–182
  29. Ariza A, Coll J, Fernández-Figueras MT, et al. Desmin myopathy: a multisystem disorder involving skeletal, cardiac, and smooth muscle. Hum Pathol. 1995;26:1032–1037
  30. Muñoz-Mármol AM, Strasser G, Isamat M, et al. A dysfunctional desmin mutation in a patient with severe generalized myopathy. Proc Natl Acad Sci U S A. 1998;95:11312–11317
  31. Park KY, Dalakas MC, Goebel HH, et al. Desmin splice variants causing cardiac and skeletal myopathy. J Med Genet. 2000;37:851–857
  32. Kjörell U, Thornell LE. Identification of a complex between alpha-actinin and the intermediate filament subunit skeletin in bovine heart Purkinje fibres. Eur J Cell Biol. 1982;28:139–144
  33. Kjörell U, Thornell LE, Lehto VP, et al. A comparative analysis of intermediate filament proteins in bovine heart Purkinje fibres and gastric smooth muscle. Eur J Cell Biol. 1987;44:68–78
  34. Thornell L, Carlsson L, Li Z, et al. Null mutation in the desmin gene gives rise to a cardiomyopathy. J Mol Cell Cardiol. 1997;29:2107–2124
  35. Milner DJ, Taffet GE, Wang X, et al. The absence of desmin leads to cardiomyocyte hypertrophy and cardiac dilation with compromised systolic function. J Mol Cell Cardiol. 1999;31:2063–2076
  36. Milner DJ, Mavroidis M, Weisleder N, et al. Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function. J Cell Biol. 2000;150:1283–1298
  37. Gard JJ, Yamada K, Green KG, et al. Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy. Cardiovasc Res. 2005;67:539–547
  38. Kaplan SR, Gard JJ, Carvajal-Huerta L, et al. Structural and molecular pathology of the heart in Carvajal syndrome. Cardiovasc Pathol. 2004;13:26–32
  39. Wang X, Osinska H, Dorn GW, et al. Mouse model of desmin-related cardiomyopathy. Circulation. 2001;103:2402–2407
  40. Asimaki A, Tandri H, Huang H, et al. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy. N Engl J Med. 2009;360:1075–1084
  41. Kaplan SR, Gard JJ, Protonotarios N, et al. Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease). Heart Rhythm. 2004;1:3–11
  42. Saffitz JE. In:  Thiene G,  Pessina AC editor. Dependence of electrical coupling on mechanical coupling in cardiac myocytes (Advances in Cardiovascular Medicine). Padua, Italy: Università degli Studi di Padova; 2003;p. 15–28
  43. Kitamura S, Ando S, Shibata M, et al. Protein kinase C phosphorylation of desmin at four serine residues within the non-alpha-helical head domain. J Biol Chem. 1989;264:5674–5678
  44. Huang X, Li J, Foster D, Lemanski SL, et al. Protein kinase C-mediated desmin phosphorylation is related to myofibril disarray in cardiomyopathic hamster heart. Exp Biol Med (Maywood). 2002;227:1039–1046
  45. Sharma S, Mücke N, Herrmann H, et al. Influence of deletions and mutations in the head domain of desmin upon assembly competence and network formation. Eur J Cell Biol. 2008;87:452

PII: S1547-5271(09)00822-4

doi: 10.1016/j.hrthm.2009.07.041

Heart Rhythm
Volume 6, Issue 11 , Pages 1574-1583 , November 2009