Genetic Evaluation of Dilated Cardiomyopathy.
ABSTRACT Recent advances have expanded our ability to conduct a comprehensive genetic evaluation for dilated cardiomyopathy (DCM). By evaluating recent literature, this review aims to bring the reader up-to-date on the genetic evaluation of DCM. Updated guidelines have been published. Mutations in BAG3, including a large deletion, were identified in 2 % of DCM. Truncating mutations in TTN were reported in 25 % of DCM. Two new genes have been reported with autosomal recessive DCM. These studies illustrate the role of improved technologies while raising the possibility of a complex genetic model for DCM. The inclusion of TTN has led to an increased genetic testing detection rate of 40 %. While our ability to identify disease-causing variants has increased, so has the identification of variants of unknown significance. A genetic evaluation for DCM must therefore address this complexity.
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ABSTRACT: Cardiomyopathy (CM) in children shares some features with cardiomyopathy in adults but also has many important unique features. Heretofore, genetic testing panels, testing strategies, and treatment recommendations have largely been based on studies in adult populations. In general, CMs in children are much more likely to be genetic and to have extracardiac manifestations that should be medically addressed. Therefore, genetic testing in children with CM is an essential part of their initial evaluation and the ongoing care of the child and family. CMs in children are more genetically heterogeneous, and many of the genes that are rare causes of CM in children are not currently included in testing panels, and future genetic testing is likely to increasingly utilize more comprehensive approaches such as whole exome/whole genome sequencing with focused analysis of all the genes that can cause CM in children.Progress in Pediatric Cardiology 01/2015; DOI:10.1016/j.ppedcard.2015.01.001
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ABSTRACT: We describe a young girl with dilated cardiomyopathy, long QT syndrome, and possible energy deficiency. Two major sequence changes were identified by whole exome sequencing (WES) and mitochondrial DNA analysis that were interpreted as potentially causative. Changes were identified in the KCNH2 gene and mitochondrial tRNA for cysteine. A variation was also seen in MYPBC3. Since the launch of WES as a clinically available technology in 2010, there has been concern regarding the identification of variants unrelated to the patient's phenotype. However, in cases where targeted sequencing fails to explain the clinical presentation, the underlying etiology could be more complex than anticipated. In this situation, the extensive reach of this tool helped explain both her phenotype and family history.06/2015; 3. DOI:10.1016/j.ymgmr.2015.03.007
Article: Inherited Cardiomyopathies[Show abstract] [Hide abstract]
ABSTRACT: Cardiomyopathies (ie, diseases of the heart muscle) are major causes of morbidity and mortality. A significant percentage of patients with cardiomyopathies have genetic-based, inheritable disease and, over the past 2 decades the genetic causes of these disorders have been increasingly discovered. The genes causing these disorders when they are mutated appear to encode proteins that frame a "final common pathway" for that specific disorder, but the specifics of the phenotype, including age of onset, severity, and outcome is variable for reasons not yet understood. The "final common pathways" for the classified forms of cardiomyopathy include the sarcomere in the primarily diastolic dysfunction disorders hypertrophic cardiomyopathy and restrictive cardiomyopathy, the linkage of the sarcomere and sarcolemma in the systolic dysfunction disorder dilated cardiomyopathy, and the desmosome in arrhythmogenic cardiomyopathy. Left ventricular noncompaction cardiomyopathy (LVNC) is an overlap disorder and it appears that any of these "final common pathways" can be involved depending on the specific form of LVNC. The genetics and mechanisms responsible for these clinical phenotypes will be described.Circulation Journal 09/2014; 78(10). DOI:10.1253/circj.CJ-14-0893 · 3.69 Impact Factor