Multiplexed Reference Materials as Controls for Cardiomyopathy Diagnostic Next-Generation Sequencing
Hypertrophic Cardiomyopathy (HCM) is a disease where the heart muscle is enlarged and a significant cause of sudden cardiac death, and is frequently asymptomatic. HCM is commonly caused by a mutation in one of nine heart muscle genes that comprise the sarcomere, and occurs at a prevalence of about 1 in 500 in the general population. HCM is the leading cause of cardiac death in young athletes in the United States.
Clinical genetic testing for mutations in the HCM-related genes has been ongoing for over a decade; the GeneTest.org database reveals 105 laboratories offering some version of genetic testing. While knowledge of prevalent pathogenic variants are available, the majority of variants remain private (that is, unpublished and not widely available). The move to NGS-based gene panels for HCM testing has lead to new challenges for test development, validation and routine quality control due to the inherent scarcity of samples, the cost of including numerous single mutations from these individual samples, and the lack of these materials for laboratories without a long history of testing.