Diagnostic yield of genetic testing in a multinational heterogeneous cohort of 2088 DCM patients.

Autor:	Heliö K; Heart and Lung Center, ERN GUARD-Heart Center, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland., Cicerchia M; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Hathaway J; Blueprint Genetics, A Quest Diagnostics Company, Seattle, USA., Tommiska J; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Huusko J; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Saarinen I; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Koskinen L; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Muona M; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Kytölä V; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Djupsjöbacka J; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Gentile M; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Salmenperä P; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Alastalo TP; Blueprint Genetics, A Quest Diagnostics Company, Seattle, USA., Steinberg C; Quebec Heart and Lung Institute, Laval University, Quebec, Canada., Heliö T; Heart and Lung Center, ERN GUARD-Heart Center, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland., Paananen J; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Myllykangas S; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland., Koskenvuo J; Blueprint Genetics, A Quest Diagnostics Company, Espoo, Finland.
Jazyk:	angličtina
Zdroj:	Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2023 Sep 19; Vol. 10, pp. 1254272. Date of Electronic Publication: 2023 Sep 19 (Print Publication: 2023).
DOI:	10.3389/fcvm.2023.1254272
Abstrakt:	Background: Familial dilated cardiomyopathy (DCM) causes heart failure and may lead to heart transplantation. DCM is typically a monogenic disorder with autosomal dominant inheritance. Currently disease-causing variants have been reported in over 60 genes that encode proteins in sarcomeres, nuclear lamina, desmosomes, cytoskeleton, and mitochondria. Over half of the patients undergoing comprehensive genetic testing are left without a molecular diagnosis even when patient selection follows strict DCM criteria. Methods and Results: This study was a retrospective review of patients referred for genetic testing at Blueprint Genetics due to suspected inherited DCM. Next generation sequencing panels included 23-316 genes associated with cardiomyopathies and other monogenic cardiac diseases. Variants were considered diagnostic if classified as pathogenic (P) or likely pathogenic (LP). Of the 2,088 patients 514 (24.6%) obtained a molecular diagnosis; 534 LP/P variants were observed across 45 genes, 2.7% (14/514) had two diagnostic variants in dominant genes. Nine copy number variants were identified: two multigene and seven intragenic. Diagnostic variants were observed most often in TTN (45.3%), DSP (6.7%), LMNA (6.7%), and MYH7 (5.2%). Clinical characteristics independently associated with molecular diagnosis were: a lower age at diagnosis, family history of DCM, paroxysmal atrial fibrillation, absence of left bundle branch block, and the presence of an implantable cardioverter-defibrillator. Conclusions: Panel testing provides good diagnostic yield in patients with clinically suspected DCM. Causative variants were identified in 45 genes. In minority, two diagnostic variants were observed in dominant genes. Our results support the use of genetic panels in clinical settings in DCM patients with suspected genetic etiology. Competing Interests: MC, JH, JT, JH, IS, LK, MM, VK, JD, MG, PS, T-PA, JP, SM and JK are full-time employees of Blueprint Genetics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 Heliö, Cicerchia, Hathaway, Tommiska, Huusko, Saarinen, Koskinen, Muona, Kytölä, Djupsjöbacka, Gentile, Salmenperä, Alastalo, Steinberg, Heliö, Paananen, Myllykangas and Koskenvuo.)
Databáze:	MEDLINE
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