A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy

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Item Type:	Article
Title:	A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy
Creators Name:	Fokstuen, S., Lyle, R., Munoz, A., Gehrig, C., Lerch, R., Perrot, A., Osterziel, K.J., Geier, C., Beghetti, M., Mach, F., Sztajzel, J., Sigwart, U., Antonarakis, S.E. and Blouin, J.L.
Abstract:	Hypertrophic cardiomyopathy (HCM) is a heterogeneous autosomal dominant cardiac disorder with a prevalence of 1 in 500. Over 450 different pathogenic mutations in at least 16 genes have been identified so far. The large allelic and genetic heterogeneity of HCM requires high-throughput, rapid, and affordable mutation detection technologies to efficiently integrate molecular screening into clinical practice. We developed a custom DNA resequencing array that contains both strands of all coding exons (160), splice-site junctions, and 5'UTR regions of 12 genes that have been clearly implicated in HCM (MYH7, MYBPC3, TNNT2, TPM1, TNNI3, MYL3, MYL2, CSRP3, PLN, ACTC, TNNC1, and PRKAG2). We analyzed a first series of 38 unrelated patients with HCM (17 familial, 21 sporadic). A total of 953,306 bp across the 38 patients were sequenced with a mean nucleotide call rate of 96.92% (range: 93-99.9%). Pathogenic mutations (single nucleotide substitutions) in MYH7, MYBPC3, TNNI3, and MYL3 (six known and six novel) were identified in 60% (10/17) of familial HCM and 10% of sporadic cases (2/21). The high-throughput HCM resequencing array is the most rapid and cost-effective tool for molecular testing of HCM to date; it thus has considerable potential in diagnostic and predictive testing, and prognostic stratification.
Keywords:	Hypertrophic Cardiomyopathy, HCM, Genetic Testing, Resequencing Array
Source:	Human Mutation
ISSN:	1059-7794
Publisher:	Wiley
Volume:	29
Number:	6
Page Range:	879-885
Date:	June 2008
Official Publication:	https://doi.org/10.1002/humu.20749
PubMed:	View item in PubMed

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