WES/WGS Reporting of Mutations from Cardiovascular "Actionable" Genes in Clinical Practice: A Key Role for UMD Knowledgebases in the Era of Big Databases

Amélie Pinard 1 David Salgado 1 Jean-Pierre Desvignes 1 Ghadi Rai 1 Nadine Hanna 2, 3 Pauline Arnaud 2, 3 Celine Guien 1 Maria Martinez 4 Laurence Faivre 5 Guillaume Jondeau 3 Catherine Boileau 2, 3 Stéphane Zaffran 1 Christophe Béroud 1 Gwenaelle Collod-Beroud 1, *
* Auteur correspondant
1 GMGF - Génétique Médicale et Génomique Fonctionnelle
2 LVTS (UMR_S_1148 / U1148) - Laboratoire de Recherche Vasculaire Translationnelle
3 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
4 IRSD - Institut de Recherche en Santé Digestive
5 GAD - Génétique des Anomalies du Développement
Abstract : High-throughput next-generation sequencing such as whole-exome and whole-genome sequencing are being rapidly integrated into clinical practice. The use of these techniques leads to the identification of secondary variants for which decisions about the reporting or not to the patient need to be made. The American College of Medical Genetics and Genomics recently published recommendations for the reporting of these variants in clinical practice for 56 "actionable" genes. Among these, seven are involved in Marfan Syndrome And Related Disorders (MSARD) resulting from mutations of the FBN1, TGFBR1 and 2, ACTA2, SMAD3, MYH11 and MYLK genes. Here, we show that mutations collected in UMD databases for MSARD genes (UMD-MSARD) are rarely reported, including the most frequent ones, in global scale initiatives for variant annotation such as the NHLBI GO Exome Sequencing Project (ESP), the Exome Aggregation Consortium (ExAC), and ClinVar. The predicted pathogenic mutations reported in global scale initiatives but absent in locus-specific databases (LSDBs) mainly correspond to rare events. UMD-MSARD databases are therefore the only resources providing access to the full spectrum of known pathogenic mutations. They are the most comprehensive resources for clinicians and geneticists to interpret MSARD-related variations not only primary variants but also secondary variants.
Keywords : ExAC Marfan syndrome LSDB ESP incidental findings marfan-syndrome variants exome pathogenicity prediction genome dissection tgfbr2 thoracic aortic-aneurysms mutations
Type de document :
Article dans une revue
Liste complète des métadonnées

Littérature citée [53 références]  Voir  Masquer  Télécharger
https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01457375
Contributeur : Gad - Université de Bourgogne <>
Soumis le : vendredi 22 décembre 2017 - 12:12:46
Dernière modification le : jeudi 20 février 2020 - 19:23:40
Archivage à long terme le : vendredi 23 mars 2018 - 12:22:38

Fichier

2016-HumMut ...
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

UNIV-BOURGOGNE | UNIV-PARIS7 | INRA | USPC | UNIV-AMU | CNRS | MMG | UNIV-PARIS13 | LVTS | UNIV-TLSE3

Citation

Amélie Pinard, David Salgado, Jean-Pierre Desvignes, Ghadi Rai, Nadine Hanna, et al.. WES/WGS Reporting of Mutations from Cardiovascular "Actionable" Genes in Clinical Practice: A Key Role for UMD Knowledgebases in the Era of Big Databases. Human Mutation, Wiley, 2016, Next Generation Sequencing and Human Genetic Disease, 37 (12), pp.1308-1317. ⟨10.1002/humu.23119⟩. ⟨hal-01457375⟩

Exporter

BibTeX TEI DC DCterms EndNote

Partager

Métriques

Consultations de la notice

535

Téléchargements de fichiers

347

Contact

Informations

CCSD