GermlineSFTPA1mutation in familial idiopathic interstitial pneumonia and lung cancer

Autor:	Serge Amselem, Alice De Ligniville, Dominique Valeyre, Nadia Nathan, Bruno Copin, Annick Clement, Nathalie Kuziner, Thierry Chinet, Valérie Nau, Florence Dastot-Le Moal, Raphael Borie, Clément Picard, Lamisse Mansour Hendili, Violaine Giraud, Hilario Nunes, Laurent Gouya, Aurore Coulomb, Louis-Jean Couderc, Bruno Crestani, Martine Reynaud Gaubert, Sylvie Tissier, Maud Simansour, Marie Legendre, Philippe Duquesnoy, Caroline Kannengiesser, Laurie Galeron
Přispěvatelé:	CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie et d'Oncologie Thoracique [AP-HP Hôpital Ambroise-Paré], Hôpital Ambroise Paré [AP-HP], Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), Université Paris 13 (UP13)-UFR SMBH, Service de pneumologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (UMRS893), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Nord [CHU - APHM], Service de pneumologie et oncologie thoracique [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre Hospitalier Universitaire Ambroise Paré (CHU Ambroise Paré), Service de Pneumologie [Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Faculté de Médecine Xavier Bichat, Service de Pneumologie et Centre de Compétence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Biochimie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de génétique et embryologie médicales [CHU Trousseau], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Service de pathologie [CHU Trousseau], COMBE, Isabelle, Service de pneumologie, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Service des maladies respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, AP-HP, Service d'Hématologie Biologique, Hôpital Robert-Debré, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Excellence GR-Ex ' The red cell : from genesis to death ', PRES Sorbonne Paris Cité
Rok vydání:	2016
Předmět:	Male 0301 basic medicine Pathology Lung Neoplasms Disease ABCA3 medicine.disease_cause Idiopathic pulmonary fibrosis 0302 clinical medicine SFTPA2 [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Missense mutation Genetics (clinical) 0303 health sciences Mutation Pulmonary Surfactant-Associated Protein A General Medicine Middle Aged respiratory system Pedigree 3. Good health medicine.anatomical_structure [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases Adenocarcinoma Female Adult medicine.medical_specialty Mutation Missense Biology 03 medical and health sciences Germline mutation Genetics medicine Humans Genetic Predisposition to Disease Idiopathic Interstitial Pneumonias Lung cancer Molecular Biology Idiopathic interstitial pneumonia Germ-Line Mutation Aged 030304 developmental biology Lung business.industry Cancer Sequence Analysis DNA medicine.disease respiratory tract diseases 030104 developmental biology Gene Expression Regulation 030228 respiratory system Immunology biology.protein business 030215 immunology
Zdroj:	Human Molecular Genetics Human Molecular Genetics, 2016, 25 (8), pp.1457-1467. ⟨10.1093/hmg/ddw014⟩ Human Molecular Genetics, Oxford University Press (OUP), 2016, 25 (8), pp.1457-1467. ⟨10.1093/hmg/ddw014⟩
ISSN:	1460-2083 0964-6906
Popis:	Background: Idiopathic interstitial pneumonia (IIP) comprise a heterogeneous group of rare lung parenchyma disorders with high morbidity and mortality. They have been associated with an increased frequency of lung cancer. A genetic cause is identified in up to 20% of familial cases, telomerase and surfactant genes (SFTPA2, SFTPB, SFTPC, ABCA3) mutations being the first etiologies. Objectives:This study investigates the implication of SFTPA1 (NM_005411) in 12 families affected by IPF and lung cancer. Methods:SFTPA1 was sequenced by Sanger method in 12 unrelated index cases. An informed signed consent was obtained for each patient. New SFTPA1 variations were studied with functional experimentations. Results: A heterozygous missense disease-causing mutation (p.Trp211Arg, W211R), in SFTPA1, that encodes the Surfactant Protein (SP)-A1, was identified in a large family. The affected members, aged 7 months to 59 years, presented with various forms of IIP, and adenocarcinoma. The W211R mutation segregated in a dominant pathway with the disease. The mutation involved an amino-acid that is located in the carbohydrate recognition domain (CRD) of SP-A1 and involved a residue invariant throughout evolution in SP-A1, but also in SP-A2 and in other CRD-containing proteins. The W211R mutation impaired SP-A1 secretion, and an abnormal expression pattern of SP-A was found in the alveolar epithelium of lung tissue from a patient carrying the SFTPA1 mutation. Conclusion: This first report of the involvement of SFTPA1 in a Mendelian disorder unveils the key role of SP-A1 in the pathophysiology of IIP from infancy to elderly, and open up a new field of research on the mechanisms involved in IIP and lung cancer.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::115e145c9af4b97be5795db26c4ecf04 https://doi.org/10.1093/hmg/ddw014 Zobrazit plný text záznamu