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Journal Article Observational Study Ppublish 2 citations

PubMed: 39260623 DOI: 10.1016/j.ijcard.2024.132542

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

Int J Cardiol 417:132542

Authors: Albert Hagège, Tania Puscas, Mohamed El Hachmi, Alessandro Parodi, Anne Bacher, Benoit Funalot, Karim Wahbi, Xavier Jeunemaître, Thibaud Damy, Clarisse Billon

Affiliations

  • 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.
  • 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.
  • 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.
  • 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.
  • AP-HP, Assistance Publique-Hôpitaux de Paris, Department of Genetics, Hôpital Henri Mondor, Créteil, 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; 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.
  • 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.
  • AP-HP, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Department of Cardiology, Créteil, 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; Department of Molecular Medicine, Sapienza University, Rome, Italy.

Abstract

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.

MeSH

Genes, Cardiology, Cardiomyopathy, Hypertrophic, Amyloidosis, Cardiomyopathies