Received on ,
Accepted on ,

Molecular Diagnostics and Genetics

Array-Based Resequencing Assay for Mutations Causing Hypertrophic Cardiomyopathy

¹ Institute for Heart and Circulation Research, University of Witten/Herdecke, Dortmund, Germany
² Institute for Human Genetics, University of Tübingen, Tübingen, Germany

^* To whom correspondence should be addressed. E-mail: waldmueller{at}herz-kreis laufforschung.de.

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 99.9%. Both techniques detected 1 heterozygous variant that was missed by the other method.

CONCLUSIONS: The data provide evidence that ABR can substrantially 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.