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Short report
Rapid detection of genetic variants in hypertrophic cardiomyopathy by custom DNA resequencing array in clinical practice
  1. Siv Fokstuen1,
  2. Analia Munoz2,
  3. Paola Melacini3,
  4. Sabino Iliceto3,
  5. Andreas Perrot4,
  6. Cemil Özcelik4,
  7. Xavier Jeanrenaud5,
  8. Claudine Rieubland6,
  9. Martin Farr7,
  10. Lothar Faber7,
  11. Ulrich Sigwart8,
  12. François Mach8,
  13. René Lerch8,
  14. Stylianos E Antonarakis1,2,
  15. Jean-Louis Blouin1
  1. 1Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland
  2. 2Department of Genetic Medicine and Development, University of Geneva School of Medicine, Geneva, Switzerland
  3. 3Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy
  4. 4Cardiology and Experimental & Clinical Research Center, Charité-Universitaetsmedizin Berlin, Germany
  5. 5Cardiology, University Hospitals of Lausanne, Lausanne, Switzerland
  6. 6Division of Human Genetics, Department of Paediatrics, University of Bern, Bern, Switzerland
  7. 7Kardiologische Klinik, Herz- und Diabeteszentrum NRW, Bad-Oeynhausen, Germany
  8. 8Cardiology, University Hospitals of Geneva, Geneva, Switzerland
  1. Correspondence to Dr Siv Fokstuen, Genetic Medicine, Centre Médical Universitaire, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland; siv.fokstuen{at}


Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease (1/500) and the most common cause of sudden cardiac death in young people. Pathogenic mutation detection of HCM is having a growing impact on the medical management of patients and their families. However, the remarkable genetic and allelic heterogeneity makes molecular analysis by conventional methods very time-consuming, expensive and difficult to realise in a routine diagnostic molecular laboratory.

Method and results The authors used their custom DNA resequencing array which interrogates all possible single-nucleotide variants on both strands of all exons (n=160), splice sites and 5′-untranslated region of 12 HCM genes (27 000 nucleotides). The results for 122 unrelated patients with HCM are presented. Thirty-three known or novel potentially pathogenic heterozygous single-nucleotide variants were identified in 38 patients (31%) in genes MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL3 and ACTC1.

Conclusions Although next-generation sequencing will replace all large-scale sequencing platforms for inherited cardiac disorders in the near future, this HCM resequencing array is currently the most rapid, cost-effective and reasonably efficient technology for first-tier mutation screening of HCM in clinical practice. Because of its design, the array is also an appropriate tool for initial screening of other inherited forms of cardiomyopathy.

  • Hypertrophic cardiomyopathy
  • genetic testing
  • resequencing array
  • mutation
  • cardiovascular medicine
  • cardiomyopathy
  • diagnostics tests
  • genetic screening/counselling
  • molecular genetics

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  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the University Hospitals of Geneva.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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