Yonago Acta medica 2009;52:121–125
Sensitivity and Specificity of Denaturing HPLC to Detect MYBPC3 Gene Mutations in Hypertrophic Cardiomyopathy
Udin Bahrudin*†, Einosuke Mizuta*, Mahayu Dewi Ariani‡, Yora Nindita* and Ichiro Hisatome*
*Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Bio-function, Tottori University Graduate School of Medical Science, Yonago 683-8503, †Center of Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang 50231, Indonesia and ‡Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, Yonago 683-8503, Japan
Denaturing high-performance liquid chromatography (DHPLC), which has recently been developed as an automated method to detect mutations, is at least ten times less expensive than the direct sequencing method; however, its sensitivity and specificity for cardiac myosin-binding protein C (MYBPC3) gene mutations in hypertrophic cardiomyopathy have not been reported yet. A mutation analysis of exons 1 to 35 of MYBPC3 gene from 20 Japanese patients with hypertrophic cardiomyopathy was performed using DHPLC and direct sequencing. Compared to direct sequencing, the sensitivity and specificity of DHPLC were 87.5% and 97.42%, respectively. Its positive and negative predictive values were 41.18% and 99.74%. The positive and negative likelihood ratios were 33.95 and 0.13, and the prevalence was 2.02%. DHPLC showed high sensitivity and specificity for detecting MYBPC3 gene mutations in hypertrophic cardiomyopathy. The use of this complementary sequencing method should reduce the cost of detection of MYBPC3 gene mutations, and could be used to screen patients with hypertrophic cardiomyopathy.
Key words: cardiac myosin-binding protein C gene; denaturing high-performance liquid chroma-tography; hypertrophic cardiomyopathy; mutation detection
