1. Rapid detection of genetic variants in hypertrophic cardiomyopathy by custom DNA resequencing array in clinical practice
- Author
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Sabino Iliceto, Cemil Özcelik, Analia Munoz, Claudine Rieubland, Stylianos E. Antonarakis, Martin Farr, Ulrich Sigwart, François Mach, Paola Melacini, René Lerch, Jean-Louis Blouin, Xavier Jeanrenaud, Siv Fokstuen, Lothar Faber, and Andreas Perrot
- Subjects
Heterozygote ,TNNT2 ,Cardiomyopathy ,030204 cardiovascular system & hematology ,Biology ,Polymorphism, Single Nucleotide ,DNA Resequencing ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Humans ,ddc:576.5 ,Genetics (clinical) ,Cardiomyopathy, Hypertrophic/genetics ,Oligonucleotide Array Sequence Analysis ,030304 developmental biology ,0303 health sciences ,ACTC1 ,Hypertrophic cardiomyopathy ,Genetic Variation ,Professional Practice ,Sequence Analysis, DNA ,Cardiomyopathy, Hypertrophic ,Polymorphism, Single Nucleotide/genetics ,medicine.disease ,3. Good health ,MYL3 ,Sequence Analysis, DNA/methods ,cardiovascular system ,MYH7 ,Allelic heterogeneity - Abstract
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.
- Published
- 2011