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The Clinical Significance of Genetic Testing in Familial Hypertrophic Cardiomyopathy

  • C. Seidman
Conference paper

Abstract

Over the past decade there has been substantial progress in understanding the molecular basis of several inherited cardiovascular disorders. Definition of the chromosome location of disease genes, identification of these genes, and characterization of different mutations within these disease genes has been the focus of many, molecular laboratories around the world. Translation of this new, fundamental genetic knowledge about human disorders, into improved clinical diagnosis and care of individuals affected by these disorders has become a new frontier in medicine. This translation is often hampered by a limited understanding by physicians of the difficulties of molecular genetic technologies and a failure by researchers to comprehend the complexities of clinical manifestations of disease. Despite these intrinsic problems, the effort of integrating basic science and medicine in hypertrophic cardiomyopathy has particular merit because the complex molecular genetics of this disease may account for the diverse clinical manifestations of this pathology. The paper will review our current understanding of the genetic basis for hypertrophie cardiomyopathy and discuss the impact this research has on clinical diagnosis and management.

Keywords

Cardiac Hypertrophy Hypertrophic Cardiomyopathy Cardiac Troponin Cardiac Myosin Essential Light Chain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Watkins H, Rosenzweig A, Hwang DS, Levi T, McKenna W, Seidman CE, Seidman JG (1992) Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med 326:1108–1114PubMedCrossRefGoogle Scholar
  2. 2.
    Watkins H, McKenna WJ, Thierfelder L, Suk J, Anan R, O’Donoghue A, Spirito P, Matsumori A, Moravec CS, Seidman JG, Seidman CE (1995) The role of cardiac troponin T and α-tropomyosin mutations in hypertrophic cardiomyopathy. N Engl J Med 332:1058–1064PubMedCrossRefGoogle Scholar
  3. 3.
    Niimura H, Bachinski LL, Watkins H, Thierfelder L, Chudley AE, Anastasakis A, Toutouzas P, Elstein E, Liew, C-C, Liew J, Rakowski H, Wigle ED, Zhao M, McKenna W, Sole M, Roberts R, Seidman JG, Seidman CE (1997) Human cardiac myosin binding protein C mutations cause late-onset familial hypertrophie cardiomyopathy; submitted.Google Scholar
  4. 4.
    Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND (1996) Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nature Genet 13:63–69PubMedCrossRefGoogle Scholar
  5. 5.
    MacRae CA, Ghaisas N, Kass S, Donnelly S, Basson CT, Watkins H, Anan R, Theirfelder LH, McGarry K, Rowland E, McKenna W, Seidman, JG, Seidman CE (1995) Familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest 96:1216–1220PubMedCrossRefGoogle Scholar
  6. 6.
    Solomon SD, Wolff S, Watkins H, Ridker PM, Come P, Seidman CE, McKenna WJ, Lee RT (1993) Left ventricular hypertrophy and morphology in familial hypertrophic cardiomyopathy associated with mutations in the β myosin heavy chain gene. J Am Coll Cardiol 22:498–505PubMedCrossRefGoogle Scholar
  7. 7.
    Maron BJ, Lipson LC, Roberts WC, Savage DD, Epstein SE (1978) “Malignant ” hypertrophic cardiomyopathy: Identification of a subgroup of families with unusually frequent premature death. Am J Cardiol 41:1133–1139PubMedCrossRefGoogle Scholar
  8. 8.
    Fananapazir L, Epstein ND (1994) Genotype-phenotype correlations in hypertrophie cardiomyopathy. Circulation 89:22–32PubMedCrossRefGoogle Scholar
  9. 9.
    Anan R, Greve G, Thierfelder L, Watkins H, McKenna WJ, Solomon S, Vecchio C, Shono H, Nakao S, Tanaka H, Mares A, Towbin JA, Spirito P, Roberts R, Seidman JG, Seidman CE (1994) Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophie cardiomyopathy. J Clin Invest 93:280.PubMedCrossRefGoogle Scholar
  10. 10.
    Coviello DA, Maron BJ, Spirito P (1996) Clinical features of hypertrophie cardiomyopathy caused by mutation of a “hot spot ” in the a tropomyosin gene. J Am Coll Cardiol 29:635–640CrossRefGoogle Scholar

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© Springer-Verlag Italia 1998

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  • C. Seidman

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