title: Array-based resequencing assay for mutations causing hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Dissecting the complex genetic basis of hypertrophic cardiomyopathy (HCM) may be key to both better understanding and optimally managing this most prevalent genetic cardiovascular disease. An array-based resequencing (ABR) assay was developed to facilitate genetic testing in HCM.
  
  
  METHODS
  An Affymetrix resequencing array and a single long-range PCR protocol were developed to cover the 3 most commonly affected genes in HCM, MYH7 (myosin, heavy chain 7, cardiac muscle, beta), MYBPC3 (myosin binding protein C, cardiac), and TNNT2 [troponin T type 2 (cardiac)].
  
  
  RESULTS
  The assay detected the underlying point mutation in 23 of 24 reference samples and provided pointers toward identifying a G insertion and a 3-bp deletion. The comparability of array-based assay results to conventional capillary sequencing was > or =99.9%. Both techniques detected 1 heterozygous variant that was missed by the other method.
  
  
  CONCLUSIONS
  The data provide evidence that ABR can substantially reduce the high workload previously associated with a genetic test for HCM. Therefore, the HCM array could facilitate large-scale studies aimed at broadening the understanding of the genetic and phenotypic diversity of HCM and related cardiomyopathies.
authors.affiliation: Institute for Heart and Circulation Research, University of Witten/Herdecke, Dortmund, Germany. waldmueller@herz-kreislaufforschung.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Waldmüller
authors.forename: Melanie
authors.initials: M
authors.lastname: Müller
authors.forename: Kirsten
authors.initials: K
authors.lastname: Rackebrandt
authors.forename: Priska
authors.initials: P
authors.lastname: Binner
authors.forename: Sven
authors.initials: S
authors.lastname: Poths
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Thomas
authors.initials: T
authors.lastname: Scheffold
mesh_terms: D024722:Cardiac Myosins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D018995:Myosin Heavy Chains / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D017422:Sequence Analysis, DNA; D020107:Troponin T / Q000235:genetics*; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D020107:Troponin T; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human