AIMS: Despite considerable progress being made in genetic diagnostics for dilated cardiomyopathy (DCM) using panels of the most prevalent genes, the cause remains unsolved in a substantial percentage of patients. We hypothesize that several previously described DCM genes with low or unknown prevalence have been neglected, which, if catalogued, could increase the yield of diagnostic DCM testing. The aim of this study is to catalogue all genetic evidence on DCM comprehensively. METHODS AND RESULTS: We have conducted a systematic literature search on PubMed, Embase, and OMIM to find genes implicated in syndromic and non-syndromic DCM and peripartum cardiomyopathy (PPCM). Our search yielded 110 nuclear protein-coding genes and 24 mitochondrial DNA genes. For nuclear genes, in addition to 42 genes sufficiently reviewed previously (group A), we provide a comprehensive annotation of the level of genetic evidence for the remaining 68 genes (group B). Next, we investigated the tissue specificity of the collected genes using public RNA sequencing data. We show that genes primarily expressed in heart and skeletal muscle are more likely to result in DCM with possible skeletal myopathies, while genes expressed ubiquitously cause DCM with extramuscular manifestations. CONCLUSION: This comprehensive analysis of DCM-associated genes revealed a much higher number of genes than currently screened in diagnostics. Since most genes in group B have only been found mutated in single DCM patients or families, their importance for DCM genetic diagnostics needs to be validated in large cohorts. Targeted sequencing of validated DCM-implicated protein-coding genes and mitochondrial DNA, together with consideration of the tissue specificity of mutated genes, may facilitate further genotype-phenotype studies in DCM.
AIMS: Despite considerable progress being made in genetic diagnostics for dilated cardiomyopathy (DCM) using panels of the most prevalent genes, the cause remains unsolved in a substantial percentage of patients. We hypothesize that several previously described DCM genes with low or unknown prevalence have been neglected, which, if catalogued, could increase the yield of diagnostic DCM testing. The aim of this study is to catalogue all genetic evidence on DCM comprehensively. METHODS AND RESULTS: We have conducted a systematic literature search on PubMed, Embase, and OMIM to find genes implicated in syndromic and non-syndromic DCM and peripartum cardiomyopathy (PPCM). Our search yielded 110 nuclear protein-coding genes and 24 mitochondrial DNA genes. For nuclear genes, in addition to 42 genes sufficiently reviewed previously (group A), we provide a comprehensive annotation of the level of genetic evidence for the remaining 68 genes (group B). Next, we investigated the tissue specificity of the collected genes using public RNA sequencing data. We show that genes primarily expressed in heart and skeletal muscle are more likely to result in DCM with possible skeletal myopathies, while genes expressed ubiquitously cause DCM with extramuscular manifestations. CONCLUSION: This comprehensive analysis of DCM-associated genes revealed a much higher number of genes than currently screened in diagnostics. Since most genes in group B have only been found mutated in single DCM patients or families, their importance for DCM genetic diagnostics needs to be validated in large cohorts. Targeted sequencing of validated DCM-implicated protein-coding genes and mitochondrial DNA, together with consideration of the tissue specificity of mutated genes, may facilitate further genotype-phenotype studies in DCM.
Authors: Elham Kayvanpour; Farbod Sedaghat-Hamedani; Ali Amr; Alan Lai; Jan Haas; Daniel B Holzer; Karen S Frese; Andreas Keller; Katrin Jensen; Hugo A Katus; Benjamin Meder Journal: Clin Res Cardiol Date: 2016-08-30 Impact factor: 5.460
Authors: Nina Nouhravesh; Gustav Ahlberg; Jonas Ghouse; Charlotte Andreasen; Jesper H Svendsen; Stig Haunsø; Henning Bundgaard; Peter E Weeke; Morten S Olesen Journal: Mol Genet Genomic Med Date: 2016-09-17 Impact factor: 2.183
Authors: Sophie Garnier; Magdalena Harakalova; Stefan Weiss; Michal Mokry; Vera Regitz-Zagrosek; Christian Hengstenberg; Thomas P Cappola; Richard Isnard; Eloisa Arbustini; Stuart A Cook; Jessica van Setten; Jorg J A Calis; Hakon Hakonarson; Michael P Morley; Klaus Stark; Sanjay K Prasad; Jin Li; Declan P O'Regan; Maurizia Grasso; Martina Müller-Nurasyid; Thomas Meitinger; Jean-Philippe Empana; Konstantin Strauch; Melanie Waldenberger; Kenneth B Marguiles; Christine E Seidman; Georgios Kararigas; Benjamin Meder; Jan Haas; Pierre Boutouyrie; Patrick Lacolley; Xavier Jouven; Jeanette Erdmann; Stefan Blankenberg; Thomas Wichter; Volker Ruppert; Luigi Tavazzi; Olivier Dubourg; Gérard Roizes; Richard Dorent; Pascal de Groote; Laurent Fauchier; Jean-Noël Trochu; Jean-François Aupetit; Zofia T Bilinska; Marine Germain; Uwe Völker; Daiane Hemerich; Ibticem Raji; Delphine Bacq-Daian; Carole Proust; Paloma Remior; Manuel Gomez-Bueno; Kristin Lehnert; Renee Maas; Robert Olaso; Ganapathi Varma Saripella; Stephan B Felix; Steven McGinn; Laëtitia Duboscq-Bidot; Alain van Mil; Céline Besse; Vincent Fontaine; Hélène Blanché; Flavie Ader; Brendan Keating; Angélique Curjol; Anne Boland; Michel Komajda; François Cambien; Jean-François Deleuze; Marcus Dörr; Folkert W Asselbergs; Eric Villard; David-Alexandre Trégouët; Philippe Charron Journal: Eur Heart J Date: 2021-05-21 Impact factor: 29.983
Authors: I H M van der Linde; Y L Hiemstra; R Bökenkamp; A M van Mil; M H Breuning; C Ruivenkamp; S W Ten Broeke; R F Veldkamp; J I van Waning; M A van Slegtenhorst; K Y van Spaendonck-Zwarts; R H Lekanne Deprez; J C Herkert; L Boven; P A van der Zwaag; J D H Jongbloed; M Bootsma; D Q C M Barge-Schaapveld Journal: Neth Heart J Date: 2017-09-01 Impact factor: 2.380