Next-Generation Sequencing for Clinical Diagnostics of Cardiomyopathies
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چکیده
Cardiomyopathies are a heterogeneous group of cardiac diseases that can either be acquired through, for example, inflammation (myocarditis), be stress-induced (tako-tsubo), or be due to a genetic cause [5,6]. Examples of genetic forms are hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy, and left-ventricular non-compaction cardiomyopathy. Together with the channellopathies, such as long-QT syndrome and Brugada syndrome, they account for the most common heart diseases and belong to the most prevalent causes of premature death in western civilizations [7,8]. A point mutation in exon 13 of the β-myosin heavy chain gene was the first detected mutation diagnosed to be relevant for HCM in 1990 [9]. Driven by this finding, genetic research has progressed tremendously over the past two decades. Mutations in genes coding for a diverse set of proteins (e.g., sarcomeric, cytoskeletal, desmosomal, channel and channel-associated, membrane, and nuclear proteins, but also mitochondrial proteins or proteins relevant for mRNA splicing) have now been found to be implicated in disease onset and progression [10]. With currently more than 90 known disease genes with more than 1000 exons and multiple malign mutations per gene, the disease’s heterogeneity is high and poses a challenge for classical Sanger-based sequencing. Although Sanger sequencing is able to detect mutations by testing only the 1
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تاریخ انتشار 2014