Waldmüller Stephan, Müller Melanie, Rackebrandt Kirsten, Binner Priska, Poths Sven, Bonin Michael, Scheffold Thomas
Institute for Heart and Circulation Research, University of Witten/Herdecke, Dortmund, Germany.
Clin Chem. 2008 Apr;54(4):682-7. doi: 10.1373/clinchem.2007.099119. Epub 2008 Feb 7.
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.
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)].
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.
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.
剖析肥厚型心肌病（HCM）复杂的遗传基础可能是更好地理解和优化管理这种最常见的遗传性心血管疾病的关键。基于芯片的重测序（ABR）检测方法被开发出来以促进HCM的基因检测。
开发了一种Affymetrix重测序芯片和一种单一的长片段PCR方案，以覆盖HCM中3个最常受累的基因，即MYH7（肌球蛋白重链7，心肌，β）、MYBPC3（心肌肌球蛋白结合蛋白C）和TNNT2[肌钙蛋白T2型（心肌）]。
该检测方法在24个参考样本中的23个中检测到了潜在的点突变，并为识别一个G插入和一个3碱基缺失提供了线索。基于芯片的检测结果与传统毛细管测序的可比性≥99.9%。两种技术都检测到了另一种方法遗漏的1个杂合变异。
数据表明ABR可以大幅减少之前与HCM基因检测相关的高工作量。因此，HCM芯片有助于开展大规模研究，以拓宽对HCM及相关心肌病的遗传和表型多样性的理解。
