Journal of Cardiac Failure
Volume 16, Issue 3 , Pages 194-199 , March 2010

Familial Dilated Cardiomyopathy Secondary to Dystrophin Splice Site Mutation

  • Dita Obler, MS

      Affiliations

    • Children's Hospital, Boston, MA
    • Corresponding Author InformationReprint requests: Dita Obler, MS, Department of Cardiology, Children's Hospital, Boston, MA 02115. Tel: 617-355-5429; Fax 011-617-730-0600.
    • ,
  • Bai-Lin Wu, PhD, M Med

      Affiliations

    • Harvard Medical School and Children's Hospital, Boston, MA
    • ,
  • Va Lip, BS

      Affiliations

    • Children's Hospital, Boston, MA
    • ,
  • Elicia Estrella, MS

      Affiliations

    • Children's Hospital, Boston, MA
    • ,
  • Sally Keck, RN, MS

      Affiliations

    • Massachusetts General Hospital, Harvard Medical School, Boston, MA
    • ,
  • Coral Haggan, RN, BSN

      Affiliations

    • Massachusetts General Hospital, Harvard Medical School, Boston, MA
    • ,
  • Marc Semigran, MD

      Affiliations

    • Massachusetts General Hospital, Harvard Medical School, Boston, MA
    • ,
  • Leslie B. Smoot, MD

      Affiliations

    • Harvard Medical School and Children's Hospital, Boston, MA

Received 4 June 2009 ,Revised 30 October 2009 ,Accepted 30 November 2009.

References 

  1. Lipshultz SE, Sleeper LA, Towbin JA, Lowe AM, Orav EJ, Cox GF, et al. The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med. 2003;348:1647–1655
  2. Manolio TA, Baughman KL, Rodeheffer R, Pearson TA, Bristow JD, Michels VV, et al. Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop). Am J Cardiol. 1992;69:1458–1466
  3. Hershberger RE, Lindenfeld J, Mestroni L, Seidman CE, Taylor MR, Towbin JA. Genetic evaluation of cardiomyopathy—a Heart Failure Society of America practice guideline. J Card Fail. 2009;15:83–97
  4. Hershberger RE, Kushner JD, Parks SB. Gene reviews: dilated cardiomyopathy overview. Last revision: March 19, 2009 [May 28, 2009]; Available from: http://www.genetests.org/servlet/access?db=geneclinics&site=gt&id=8888891&key=clzhsDT00Sb2H&gry=&fcn=y&fw=CL0C&filename=/profiles/dcm-ov/index.html. Accessed December 14, 2009.
  5. Baig MK, Goldman JH, Caforio AL, Coonar AS, Keeling PJ, McKenna WJ. Familial dilated cardiomyopathy: cardiac abnormalities are common in asymptomatic relatives and may represent early disease. J Am Coll Cardiol. 1998;31:195–201
  6. Hanson EL, Hershberger RE. Genetic counseling and screening issues in familial dilated cardiomyopathy. J Genet Couns. 2001;10:397–415
  7. Burkett EL, Hershberger RE. Clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol. 2005;45:969–981
  8. Feng J, Yan JY, Buzin CH, Sommer SS, Towbin JA. Comprehensive mutation scanning of the dystrophin gene in patients with nonsyndromic X-linked dilated cardiomyopathy. J Am Coll Cardiol. 2002;40:1120–1124
  9. Cohen N, Muntoni F. Multiple pathogenetic mechanisms in X linked dilated cardiomyopathy. Heart. 2004;90:835–841
  10. Bennett RR, den Dunnen J, O'Brien KF, Darras BT, Kunkel LM. Detection of mutations in the dystrophin gene via automated DHPLC screening and direct sequencing. BMC Genet. 2001;2:17
  11. Milasin J, Muntoni F, Severini GM, Bartoloni L, Vatta M, Krajinovic M, et al. A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy. Hum Mol Genet. 1996;5:73–79
  12. Kimura S, Ikezawa M, Ozasa S, Ito K, Ueno H, Yoshioka K, et al. Novel mutation in splicing donor of dystrophin gene first exon in a patient with dilated cardiomyopathy but no clinical signs of skeletal myopathy. J Child Neurol. 2007;22:901–906
  13. Arbustini E, Diegoli M, Morbini P, Dal Bello B, Banchieri N, Pilotto A, et al. Prevalence and characteristics of dystrophin defects in adult male patients with dilated cardiomyopathy. J Am Coll Cardiol. 2000;35:1760–1768
  14. Feng J, Yan J, Buzin CH, Towbin JA, Sommer SS. Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy. Mol Genet Metab. 2002;77:119–126
  15. Politano L, Nigro V, Nigro G, Petretta VR, Passamano L, Papparella S, et al. Development of cardiomyopathy in female carriers of Duchenne and Becker muscular dystrophies. JAMA. 1996;275:1335–1338
  16. Towbin JA, Hejtmancik JF, Brink P, Gelb B, Zhu XM, Chamberlain JS, et al. X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Circulation. 1993;87:1854–1865
  17. Muntoni F, Cau M, Ganau A, Congiu R, Arvedi G, Mateddu A, et al. Brief report: deletion of the dystrophin muscle-promoter region associated with X-linked dilated cardiomyopathy. N Engl J Med. 1993;329:921–925
  18. Muntoni F, Wilson L, Marrosu G, Marrosu MG, Cianchetti C, Mestroni L, et al. A mutation in the dystrophin gene selectively affecting dystrophin expression in the heart. J Clin Invest. 1995;96:693–699
  19. Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, et al. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. N Engl J Med. 1988;318:1363–1368
  20. Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003;2:731–740
  21. Bastianutto C, Bestard JA, Lahnakoski K, Broere D, De Visser M, Zaccolo M, et al. Dystrophin muscle enhancer 1 is implicated in the activation of non-muscle isoforms in the skeletal muscle of patients with X-linked dilated cardiomyopathy. Hum Mol Genet. 2001;10:2627–2635
  22. Ferlini A, Sewry C, Melis MA, Mateddu A, Muntoni F. X-linked dilated cardiomyopathy and the dystrophin gene. Neuromuscul Disord. 1999;9:339–346
  23. Jefferies JL, Eidem BW, Belmont JW, Craigen WJ, Ware SM, Fernbach SD, et al. Genetic predictors and remodeling of dilated cardiomyopathy in muscular dystrophy. Circulation. 2005;112:2799–2804
  24. Bostick B, Yue Y, Long C, Marschalk N, Fine DM, Chen J, et al. Cardiac expression of a mini-dystrophin that normalizes skeletal muscle force only partially restores heart function in aged Mdx mice. Mol Ther. 2009;17:253–261
  25. McNally EM. New approaches in the therapy of cardiomyopathy in muscular dystrophy. Annu Rev Med. 2007;58:75–88
  26. Townsend D, Yasuda S, Li S, Chamberlain JS, Metzger JM. Emergent dilated cardiomyopathy caused by targeted repair of dystrophic skeletal muscle. Mol Ther. 2008;16:832–835

 Supported in part by the Cardiology Foundation at Children's Hospital, Boston.

PII: S1071-9164(09)01198-1

doi: 10.1016/j.cardfail.2009.11.009

Journal of Cardiac Failure
Volume 16, Issue 3 , Pages 194-199 , March 2010

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