Modern genomic techniques in the identification of genetic causes of cardiomyopathy.

Autor:	Spracklen TF; Cape Heart Institute, University of Cape Town Department of Medicine, Cape Town, South Africa.; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa., Keavney B; Division of Cardiovascular Sciences, The University of Manchester, Manchester, UK., Laing N; Division of Human Genetics, University of Cape Town, Cape Town, South Africa., Ntusi N; Cape Heart Institute, University of Cape Town Department of Medicine, Cape Town, South Africa.; Department of Medicine, University of Cape Town, Cape Universities Body Imaging Centre, Cape Town, South Africa., Shaboodien G; Cape Heart Institute, University of Cape Town Department of Medicine, Cape Town, South Africa gasnat.shaboodien@uct.ac.za.
Jazyk:	angličtina
Zdroj:	Heart (British Cardiac Society) [Heart] 2022 Nov 10; Vol. 108 (23), pp. 1843-1850. Date of Electronic Publication: 2022 Nov 10.
DOI:	10.1136/heartjnl-2021-320424
Abstrakt:	Over the past three decades numerous disease-causing genes have been linked to the pathogenesis of heritable cardiomyopathies, but many causal genes are yet to be identified. Next-generation sequencing (NGS) platforms have revolutionised clinical testing capacity in familial cardiomyopathy. In this review, we summarise how NGS technologies have advanced our understanding of genetic non-syndromic cardiomyopathy over the last decade. First, 26 putative new disease-causing genes have been identified to date, mostly from whole-exome sequencing, and some of which ( FLNC , MTO1 , HCN4 ) have had a considerable clinical impact and are now included in routine diagnostic gene panels. Second, we consider challenges in variant interpretation and the importance of large-scale NGS population control cohorts for this purpose. Third, an emerging role of common variation in some forms of genetic cardiomyopathy is being elucidated through recent studies which have illustrated an additive effect of numerous polymorphic loci on cardiac parameters; this may explain phenotypic variability and low rates of genetic diagnosis from sequencing studies. Finally, we discuss the clinical utility of genetic testing in cardiomyopathy in Western settings, where NGS panel testing of core disease genes is currently recommended with possible implications for patient management. Given the findings of recent studies, whole-exome or whole-genome sequencing should be considered in patients of non-European ancestry with clearly familial disease, or severe paediatric disease, when no result is obtained on panel sequencing. The clinical utility of polygenic risk assessment needs to be investigated further in patients with unexplained dilated cardiomyopathy and hypertrophic cardiomyopathy in whom a pathogenic variant is not identified. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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