Advertisement

Molecular Genetics in Cardiology

  • M. M. A. M. Mannens
  • H. J. M. Smeets
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 239)

Abstract

Genetics and genomics are being introduced rapidly into clinical practice. Knowledge on genes and gene defects, gene expression and gene products are being gathered as part of the recently completed human genome project at a rapid pace [1,2]. The genetic cause of the vast majority of important monogenie disorders is known, the more rare disorders are being unravelled fast. Technical developments enable molecular geneticists an accelerated and detailed characterization of genetic defects, predisposition or background of individual patients. The introduction of genetic tests for heritable cardiac abnormalities is of a recent nature. Disorders, like the Long QT-syndrome, Brugada syndrome or hypertrophic and dilated cardiomyopathies have only recently been unravelled and research is ongoing to improve DNA-diagnostics [3,4], Genetic testing offers many opportunities, but also a considerable number of risks and uncertainties, and introduction in the clinic has to be performed with great care. Not every test that can be done, should be done. It is evident that genetic testing must be beneficial for the patient. If he or she is affected, then the test can either be performed to make or confirm a diagnosis or to predict prognosis and adjust treatment. It is clear that a genetic test affects not only the patient involved, but also concems relatives or future off spring. Even if patients are unaffected, it is possible to determine their genetic status and to predict what the chances will be of developing symptoms in the years to follow.

Keywords

Genetic Testing Gene Defect Familial Hypercholesterolemia Brugada Syndrome Monogenic Disorder 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    International Human Genome Consortium. Initial sequencing and analysis of the human genome. Nature 2001; 409:860–921.CrossRefGoogle Scholar
  2. 2.
    Venter J.C., Adams M.D., Myers E.M., et al. The sequence of the human genome. Science 2001; 291:1304–51.Google Scholar
  3. 3.
    Priori S.G., Barhanin J., Hauer R.N.W., et al. Genetic and molecular basis of cardiac arrhythmias: impact on clinical management. Part 1 and 11. Circulation 1999; 99:518–28.PubMedCrossRefGoogle Scholar
  4. 4.
    Jongbloed R.J.E., Wilde A.A.M., Geelen J.L.M.C., et al. Novel KCNQ1 and HERG missense mutations in Dutch Long-QT families. Hum Mutat 1999; 13:301–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Strachan T., Read A.P. Human Molecular Genetics; 2nd edition. Oxford: Bios Scientific Publishers 1999.Google Scholar
  6. 6.
    Priori S.G., Napolitano C., Schwartz P.J. Low penetrance in the Long-QT syndrome. Clinical impact. Circulation 1999; 99:529–33.Google Scholar
  7. 7.
    Priori S.G. Long QT and Brugada syndromes: from genetics to clinical management. J Cardiovasc Electrophysiol 2000; 11: 1174–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Bezzina C., Veldkamp M.W., Van den Berg M.P., et al. A single Na+ channel mutation causing both long-QT and Brugada syndromes. Circ Res 1999; 85: 1206–13.PubMedCrossRefGoogle Scholar
  9. 9.
    Bezzina C.R., Rook M.B., Wilde A.A.M. Cardiac sodium channel and inherited arrhythmia syndromes. Cardiovasc Res 2001; 49:257–71.PubMedCrossRefGoogle Scholar
  10. 10.
    Neyroud N., Tesson F., Denjoy I., et al. A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat Genet 1997; 15:186–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Towbin J.A., Lipshultz S.E. Genetics of neonatal cardiomyopathy. Curr Op Cardiol 1999; 14:250–62.CrossRefGoogle Scholar
  12. 12.
    Reik W., Walter J. Genomic imprinting: parental influence on the genome. Nat Rev Genet 2001; 2:21–32.Google Scholar
  13. 13.
    Haines J.I., Pericak-Vance M.A., eds. Approaches to gene mapping in complex human diseases. New York: Wiley-Liss 1998.Google Scholar
  14. 14.
    Bonne G., Carrier L., Richard P., Hainque B., Schwartz K. Familial Hypertrophic Cardiomyopathy. From mutations to functional defects. Circ Res 1998; 83:580–93.PubMedCrossRefGoogle Scholar
  15. 15.
    Nicol R.L., Frey N., Olson E.N. From the sarcomere to the nucleus: Role of genetics and signaling in structural heart disease. Annu. Rev. Genomics Hum Genet 2000; 01: 179–223.CrossRefGoogle Scholar
  16. 16.
    Wilde A.A.M., Roden D.M. Predicting the long-QT genotype from clinical data. From sense to science. Circulation 2000; 102:2796–8.Google Scholar
  17. 17.
    Hawkins J.R. Finding mutations, the basics. Oxford University Press 1997.Google Scholar
  18. 18.
    DeCoo I.F.M., Gussinklo T., Arts P.J.W., Oost van B.A., Smeets HJM. A PCR test for progressive extemal ophthalmoplegia and Keams-Sayre syndrome on DNA from blood sampies. J Neur Sci 1997; 149:37–40.CrossRefGoogle Scholar
  19. 19.
    Underhill P.A., Jin L., Lin A.A., et al, Detection of numerous Y chromosome biallelic polymorphisms by denaturing high-performance liquid chromatography. Genome Res 1997; 10:996–1005.Google Scholar
  20. 20.
    Bosch van den B.J.C., Coo de R.F.M, Scholte H.R., et al. Mutation analysis of the entire mitochondrial genome using denaturing high performance liquid chromatography. Nucl Acids Res 2000; 28:89–96.CrossRefGoogle Scholar
  21. 21.
    Lipshutz R.J., Fodor S.P.A., Gingeras T.R., Lockhart D.J. High density synthetic oligonucleotide arrays. Nature Genet 1999 21 suppl:20–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Young R.A. Biomedical discovery with DNA arrays. Cell 2000; 102:9–15.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2001

Authors and Affiliations

  • M. M. A. M. Mannens
  • H. J. M. Smeets

There are no affiliations available

Personalised recommendations