The French hypertrophic cardiomyopathy gene register: A systematic large gene screening for hypertrophic cardiomyopathy.

Autor: Hagège A; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiology, Paris, France; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Centre de Référence des Cardiomyopathies et des Troubles du Rythme Cardiaque Héréditaires ou Rares, Paris, France; Université de Paris, INSERM U 970, Paris Cardiovascular Research Centre, Paris, France, Paris, France. Electronic address: albert.hagege@aphp.fr., Puscas T; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiology, Paris, France; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Centre de Référence des Cardiomyopathies et des Troubles du Rythme Cardiaque Héréditaires ou Rares, Paris, France., El Hachmi M; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Centre de Référence des Cardiomyopathies et des Troubles du Rythme Cardiaque Héréditaires ou Rares, Paris, France; Université de Paris, INSERM U 970, Paris Cardiovascular Research Centre, Paris, France, Paris, France; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Genetics, Paris, France; Department of Molecular Medicine, Sapienza University, Rome, Italy., Parodi A; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiology, Paris, France; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Centre de Référence des Cardiomyopathies et des Troubles du Rythme Cardiaque Héréditaires ou Rares, Paris, France; Università del Piemonte Orientale, Vercelli, Italy., Bacher A; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiology, Paris, France; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Centre de Référence des Cardiomyopathies et des Troubles du Rythme Cardiaque Héréditaires ou Rares, Paris, France., Funalot B; AP-HP, Assistance Publique-Hôpitaux de Paris, Department of Genetics, Hôpital Henri Mondor, Créteil, France., Wahbi K; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Centre de Référence des Cardiomyopathies et des Troubles du Rythme Cardiaque Héréditaires ou Rares, Paris, France; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Genetics, Paris, France; Université de Paris, AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Department of Cardiology, Paris, France., Jeunemaître X; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Centre de Référence des Cardiomyopathies et des Troubles du Rythme Cardiaque Héréditaires ou Rares, Paris, France; Université de Paris, INSERM U 970, Paris Cardiovascular Research Centre, Paris, France, Paris, France; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Genetics, Paris, France., Damy T; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Department of Cardiology, Créteil, France., Billon C; AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Centre de Référence des Cardiomyopathies et des Troubles du Rythme Cardiaque Héréditaires ou Rares, Paris, France; Université de Paris, INSERM U 970, Paris Cardiovascular Research Centre, Paris, France, Paris, France; Department of Molecular Medicine, Sapienza University, Rome, Italy.
Jazyk: angličtina
Zdroj: International journal of cardiology [Int J Cardiol] 2024 Dec 15; Vol. 417, pp. 132542. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1016/j.ijcard.2024.132542
Abstrakt: Background: Although the optimal approach is debated, systematic genetic screening for hypertrophic cardiomyopathy (HCM) is recommended.
Aims: The performance of this approach was tested in GEREMY, a HCM prospective observational French register.
Methods: Screening was based on a 12-gene panel, including the Fabry disease (GLA) and the transthyretin (TTR) genes. In case of a negative result and according to the clinical profile, 17-80 gene panels of were used.
Results: A 748 adult cohort was examined: 68.9 % male, 54.6 ± 18.1 years, 27.5 % with a HCM family history, maximal wall thickness 19.1 ± 4.8 mm. Pathogenic or likely pathogenic variants were identified in 296 (39.6 %) patients, localized 1) in sarcomeric genes in 233, most frequently MYBPC3 (150) and MYH7 (42), with 24 identified only by large panels, with multiple variants in 8 patients and 2) in non-sarcomeric genes in 63, identified only with large panels in 26, predominantly TTR (26) and GLA(9), representing 8.8 % and 3.0 % of positive studies, respectively. Performance was 57.1 % before 40 years and 68.6 % in case of FH (vs otherwise 28.7 % and 26.1 % respectively, p < 0.001). In patients with a negative study, 148 had variants of unknown significance and 95 had senile or AL amyloidosis.
Conclusions: Systematic genetic screening with a limited panel showed good performance, with diagnosis of Fabry disease (∼1 %) and hereditary TTR amyloidosis (∼3.5 %). Larger targeted panels were conclusive in 35.3 % of patients, of which 12 % had a negative initial approach.
Competing Interests: Declaration of competing interest Pr. Hagege has served as an advisor to Alnylam, Amicus, Bristol Myers Squibb, Cytokinetics, Gilead, Myokardia, Pfizer, Sanofi Genzyme, Tenaya.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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