Rapid detection of genetic variants in hypertrophic cardiomyopathy by custom DNA resequencing array in clinical practice

Item Type:	Article
Title:	Rapid detection of genetic variants in hypertrophic cardiomyopathy by custom DNA resequencing array in clinical practice
Creators Name:	Fokstuen, S. and Munoz, A. and Melacini, P. and Iliceto, S. and Perrot, A. and Ozcelik, C. and Jeanrenaud, X. and Rieubland, C. and Farr, M. and Faber, L. and Sigwart, U. and Mach, F. and Lerch, R. and Antonarakis, S.E. and Blouin, J.L.
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.
Keywords:	Hypertrophic Cardiomyopathy, Genetic Variation, Heterozygote, Oligonucleotide Array Sequence Analysis, Single Nucleotide Polymorphism , Professional Practice, DNA Sequence Analysis
Source:	Journal of Medical Genetics
ISSN:	0022-2593
Publisher:	BMJ Publishing Group
Volume:	48
Number:	8
Page Range:	572-576
Date:	August 2011
Official Publication:	https://doi.org/10.1136/jmg.2010.083345
PubMed:	View item in PubMed

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