This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.

Genetic biomarkers are crucial for diagnosis, guiding of treatments and estimation of prognosis. In the past, clinical genetic diagnostics was limited by the sequencing information gained from selected exons and single genes. For genetically heterogeneous diseases, such as cardiomyopathies, where underlying mutations in more than 1000 exons are known, a Sanger-based comprehensive test would have been extremely expensive and labor intensive. Next-generation sequencing has overcome these problems in terms of costs, speed and throughput. In this review we discuss available methods for targeted next-generation sequencing that ease the introduction of this technology into routine clinical application. We further provide results of a study we have performed to compare two state-of-the-art methods for their enrichment efficiency and detection accuracy of variants in a clinical setting.

Cardiovascular diseases are among the major causes of morbidity and mortality worldwide. Currently, considerable effort is made to intensify preventive measures, refi ne diagnostic testing, and advance therapeutic strategies. In this context, miRNAs have emerged as a new class of key regulators involved in the pathogenesis of many cardiovascular disorders, entailing a deep scientifi c interest in assessing their biomedical potential. Numerous studies identifi ed miRNA signatures that correlate with specifi c cardiovascular conditions, hereby emphasizing their potential as molecular biomarkers. In the therapeutic setting, modulations of miRNA expression and function in experimental models of cardiac hypertrophy and heart failure are promising approaches. The encouraging results of these proof-of-concept studies and fi rst successful clinical trials in humans point to a bright future for miRNAs in cardiovascular medicine.