Array-based resequencing assay for mutations causing hypertrophic cardiomyopathy.
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.
Waldmüller
Stephan
S
Institute for Heart and Circulation Research, University of Witten/Herdecke, Dortmund, Germany. waldmueller@herz-kreislaufforschung.de
Müller
Melanie
M
Rackebrandt
Kirsten
K
Binner
Priska
P
Poths
Sven
S
Bonin
Michael
M
Scheffold
Thomas
T
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
D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D020107:Troponin T; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human