Scientific article

A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy

Published inHuman mutation, vol. 29, no. 6, p. 879-885
Publication date2008

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.

  • Cardiomyopathy, Hypertrophic/diagnosis/genetics
  • Cardiomyopathy, Hypertrophic, Familial/diagnosis
  • DNA Mutational Analysis
  • Humans
  • Mutation
  • Oligonucleotide Array Sequence Analysis/economics/methods
Citation (ISO format)
FOKSTUEN, Siv et al. A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy. In: Human mutation, 2008, vol. 29, n° 6, p. 879–885. doi: 10.1002/humu.20749
Main files (1)
Article (Accepted version)
ISSN of the journal1059-7794

Technical informations

Creation03/03/2009 11:08:00 AM
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