Widening the landscape of heritable pulmonary hypertension mutations in paediatric and adult cases.


Journal

The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460

Informations de publication

Date de publication:
03 2019
Historique:
received: 25 04 2018
accepted: 23 11 2018
pubmed: 24 12 2018
medline: 10 10 2020
entrez: 23 12 2018
Statut: epublish

Résumé

Heritable forms of pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH) diverge by lung histopathological lesions, clinical and para-clinical presentation, their responsible genes, and mode of transmission. Since the identification of the We set up a next-generation sequencing-based targeted sequencing gene panel allowing known genes for PAH and PVOD/PCH to be analysed simultaneously Pathogenic mutations were identified in 19.5% of sporadic PAH patients (n=180), 54.5% of familial PAH patients and 13.3% of PVOD/PCH patients. Our results confirm that mutations are found in genes beyond

Sections du résumé

BACKGROUND
Heritable forms of pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH) diverge by lung histopathological lesions, clinical and para-clinical presentation, their responsible genes, and mode of transmission. Since the identification of the
METHODS
We set up a next-generation sequencing-based targeted sequencing gene panel allowing known genes for PAH and PVOD/PCH to be analysed simultaneously
RESULTS
Pathogenic mutations were identified in 19.5% of sporadic PAH patients (n=180), 54.5% of familial PAH patients and 13.3% of PVOD/PCH patients.
CONCLUSION
Our results confirm that mutations are found in genes beyond

Identifiants

pubmed: 30578383
pii: 13993003.01371-2018
doi: 10.1183/13993003.01371-2018
pii:
doi:

Substances chimiques

BMP10 protein, human 0
Bone Morphogenetic Proteins 0
GDF2 protein, human 0
Growth Differentiation Factor 2 0
T-Box Domain Proteins 0
TBX4 protein, human 0
BMPR2 protein, human EC 2.7.11.30
Bone Morphogenetic Protein Receptors, Type II EC 2.7.11.30

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright ©ERS 2019.

Déclaration de conflit d'intérêts

Conflict of interest: M. Eyries reports personal fees from Roche Diagnostics France, during the conduct of the study. Conflict of interest: D. Montani reports personal fees from Actelion, GSK, MSD and Pfizer, outside the submitted work. Conflict of interest: S. Nadaud has nothing to disclose. Conflict of interest: B. Girerd has nothing to disclose. Conflict of interest: M. Levy has nothing to disclose. Conflict of interest: A. Bourdin reports grants, personal fees for speaking and nonfinancial support from GSK, grants, personal fees for speaking and advisory board work, and nonfinancial support from AstraZeneca and Boehringer Ingelheim, personal fees for speaking and advisory board work, and nonfinancial support from Novartis, grants from MSD, grants and personal fees for speaking from Actelion, and personal fees for speaking and nonfinancial support from Chiesi Farmaceuticals, outside the submitted work. Conflict of interest: R. Trésorier has nothing to disclose. Conflict of interest: A. Chaouat has nothing to disclose. Conflict of interest: V. Cottin reports personal fees for consultancy, lectures and travel to medical meetings from Actelion and Roche, personal fees for development of educational presentations, consultancy, lectures and travel to medical meetings from Boehringer Ingelheim, personal fees for consultancy from Bayer, personal fees for adjudication committee work from Gilead, personal fees for consultancy and travel to medical meetings from MSD, personal fees for consultancy and lectures from Novartis and Sanofi, institutional grants from Boehringer Ingelheim and Roche, personal fees for data and safety monitoring board work from Promedior and Celgene, and personal fees for consultancy and data and safety monitoring board work from Galapagos, outside the submitted work. Conflict of interest: C. Sanfiorenzo has nothing to disclose. Conflict of interest: G. Prevot has nothing to disclose. Conflict of interest: M. Reynaud-Gaubert has nothing to disclose. Conflict of interest: C. Dromer has nothing to disclose. Conflict of interest: A. Houeijeh has nothing to disclose. Conflict of interest: K. Nguyen has nothing to disclose. Conflict of interest: F. Coulet has nothing to disclose. Conflict of interest: D. Bonnet reports personal fees for advisory board work from Actelion Pharmaceuticals, Bayer Health Care and Novartis, outside the submitted work. Conflict of interest: M. Humbert reports personal fees from Actelion, Bayer, GSK, Johnson & Johnson, Merck and United Therapeutics, outside the submitted work. Conflict of interest: F. Soubrier has nothing to disclose.

Auteurs

Mélanie Eyries (M)

Département de Génétique, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France.
UMR_S1166, Sorbonne Université, INSERM, and Institute for Cardiometabolism and Nutrition (ICAN), Paris, France.

David Montani (D)

Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire, INSERM UMR_S999, Hôpital de Bicêtre, AP-HP, Le Kremlin-Bicêtre, France.

Sophie Nadaud (S)

UMR_S1166, Sorbonne Université, INSERM, and Institute for Cardiometabolism and Nutrition (ICAN), Paris, France.

Barbara Girerd (B)

Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire, INSERM UMR_S999, Hôpital de Bicêtre, AP-HP, Le Kremlin-Bicêtre, France.

Marilyne Levy (M)

M3C-Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.

Arnaud Bourdin (A)

PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France.
Département de Pneumologie et Addictologie, CHU Montpellier, Montpellier, France.

Romain Trésorier (R)

Service de Cardiologie Maladies Vasculaires, CHU Gabriel Montpied, Clermont-Ferrand, France.

Ari Chaouat (A)

Département de Pneumologie, CHRU Nancy, Université de Lorraine, INSERM U1116, Nancy, France.

Vincent Cottin (V)

Service de Pneumologie, Centre National de Référence des Maladies Pulmonaires Rares, Hôpital Louis Pradel, Université Claude Bernard Lyon 1, UMR754, Lyon, France.

Céline Sanfiorenzo (C)

Service de Pneumologie, Hôpital Pasteur, CHU Nice, Nice, France.

Grégoire Prevot (G)

Service de Pneumologie, Hôpital Larrey, Toulouse, France.

Martine Reynaud-Gaubert (M)

Service de Pneumologie, CHU Nord de Marseille, AP-HM, Marseille, France.

Claire Dromer (C)

Service de Pneumologie, CHU de Bordeaux Hôpital Haut-Levêque, Pessac, France.

Ali Houeijeh (A)

Service de Cardiologie Infantile et Congénitale, CHRU Lille-Hôpital Cardiologique, Lille, France.

Karine Nguyen (K)

Département de Génétique Médicale, CHU la Timone Enfants, AP-HM, Marseille, France.

Florence Coulet (F)

Département de Génétique, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France.

Damien Bonnet (D)

M3C-Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.

Marc Humbert (M)

Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire, INSERM UMR_S999, Hôpital de Bicêtre, AP-HP, Le Kremlin-Bicêtre, France.

Florent Soubrier (F)

Département de Génétique, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France.
UMR_S1166, Sorbonne Université, INSERM, and Institute for Cardiometabolism and Nutrition (ICAN), Paris, France.

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Classifications MeSH