Contribution of mutations in genes of the surfactant system to idiopathic interstitial pneumonia (IIP)

Nadia Nathan (1) , Marie Legendre (2) , Emilie Filhol-Blin (3) , Raphael Borie (4) , Diane Bouvry (5) , Mickael Afanetti (6) , Kais Ahmad , Juliette Albuisson (7) , Nathalie Allou , Carole Bailly (8) , Keren Borensztajn (9) , Afifaa Butt , Bruno Copin (10) , Aurore Coulomb L'Hermine , Bruno Crestani (11) , Jean-Charles Dalphin (12) , Marie-Laure Dalphin (13) , Florence Dastot Le Moal (10) , Christophe Delacourt (14) , Bertrand Delaisi (15) , Antoine Deschildre (16) , Paul de Vuyst (17) , Bruno Diot (18) , Claire Dromer (19) , Jean-Christophe Dubus (20) , Philippe Duquesnoy (2) , Lisa Giovannini-Chami (21) , Violaine Giraud (22) , Carine Gomez (23) , Anne Gondouin (24) , Laurent Gouya (25) , Alice Hadchouel (26) , Sandrine Hirschi (27) , Véronique Houdouin (28) , Dominique Israel Biet , Caroline Kannengiesser (29) , Claire Lefèvre , Effrosyne Manali (30) , Sylvain Marchand-Adam (31) , Christophe Marguet (32) , Jean-Marc Naccache (33) , Valerie Nau , Hilario Nunes (34) , Oisin O'Connell , Katherine O'Reilly , Spyros Papiris (30) , Clement Picard (35) , Grégoire Prévot (36) , Philippe Reix (37) , Martine Reynaud-Gaubert (38, 39) , Elisabeth Rivaud (35) , Elise Schaefer (40) , Aurélie Tatopoulos (41) , Julie Traclet (42) , Françoise Troussier (43) , Dominique Valeyre (5) , Vincent Cottin (44) , Annick Clement (45) , Serge Amselem (2)

1 UMRS893 - Centre de Recherche Saint-Antoine
2 Physiopathologie des maladies génétiques d'expression pédiatrique
3 U933 - Maladies génétiques d'expression pédiatrique
4 PHERE (UMR_S_1152 / U1152) - Physiopathologie et Epidémiologie des Maladies Respiratoires
5 Service de pneumologie [Avicenne]
6 CHU Nice - Centre Hospitalier Universitaire de Nice
7 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
8 Centre de Recherches de Gonfreville
9 Département Hospitalo-universtaire FIRE (Fibrosis, Inflammation and Remodeling)
10 CHU Trousseau [APHP]
11 LabEx Inflamex
12 LCE - Laboratoire Chrono-environnement (UMR 6249)
13 Service de pédiatrie [CHRU Besançon]
14 LDO - Domaines Océaniques
15 Service de gastro-entérologie, mucoviscidose, pneumologie et nutrition[Debré]
16 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
17 ULB - Hôpital Erasme [Bruxelles]
18 AGIM - AGeing and IMagery
19 Service Maladies Respiratoires
20 Service de pneumologie pédiatrique
21 IPMC - Institut de pharmacologie moléculaire et cellulaire
22 Service de Pneumologie et d'Oncologie Thoracique [AP-HP Hôpital Ambroise-Paré]
23 Hôpital Nord [CHU - APHM]
24 Service de Pneumologie, oncologie thoracique et allergologie respiratoire [CHRU Besançon]
25 CRB3 - Centre de recherche biomédicale Bichat-Beaujon
26 Service de Pneumologie Allergologie [CHU Necker]
27 Service de pneumologie (Strasbourg)
28 Service de pneumologie pédiatrique
29 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
30 NKUA - National and Kapodistrian University of Athens
31 PRPA - Pathologies Respiratoires : Protéolyse et Aérosolthérapie
32 UNIROUEN - Université de Rouen Normandie
33 CHU Tenon [AP-HP]
34 H&P - Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires
35 Hôpital Foch [Suresnes]
36 Competence Center for Rare Pulmonary Diseases
37 Service de Pédiatrie, Pneumologie, Allergologie et Mucoviscidose
38 MEPHI - Microbes évolution phylogénie et infections
39 APHM - Assistance Publique - Hôpitaux de Marseille
40 LGM - Laboratoire de Génétique Médicale
41 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
42 Hôpital Louis Pradel - Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie
43 Service de Pneumologie Pédiatrique [Angers]
44 Department of Pneumology [Lyon]
45 CRSA - Centre de Recherche Saint-Antoine

Background: Children and adult IIP are heterogeneous and severe disorders. Whereas telomerase gene mutations are preferentially found in adult IIP, surfactant gene mutations are mainly reported in children. The study aimed to assess the contribution of surfactant gene mutations in a large pediatric and adult IIP cohort.
Methods: Patients with IIP were prospectively included in the French network of rare lung diseases centres. All SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3, NKX2-1 exons and flanking intronic sequences were analyzed. The identified variations were assessed in silico. Only pathogenic or likely pathogenic mutations were taken into account.
Results: 477 patients were included in 4 years (190 children; 287 adults). The mean age at diagnosis was 40 years (0-100) and the sex ratio was 1.47 M/F. The IIP was familial in 22% of cases. A personal or family history of lung cancer was found in 44 (15%) adults. A mutation was identified in a surfactant gene in 45 (9.4%) patients, including 22 (11.6%) children and 23 (8%) adults. Mutations were identified in all the studied genes in children and in adults, except for a SFTPB mutation identified in an adult. A mutation was found in 25% of the 44 adults with a history of IIP and lung cancer (SFTPA = 10, SFTPC = 1).
Discussion and conclusion: Surfactant gene mutations encounter for an important part of IIP, thereby strongly suggesting that these molecular analyses should be part of the diagnosis process of IIP, regardless of the patient’s age, especially in case of family history of IIP and/or lung cancer. Such systematic approach should help guiding the most relevant genetic tests to be performed according to the disease phenotype.

This is an ERS International Congress abstract. No full-text version is available.

Domaines: Bactériologie; Virologie; Parasitologie; Cardiologie et système cardiovasculaire; Maladies émergentes; Maladies infectieuses

Nadia Nathan, Marie Legendre, Emilie Filhol-Blin, Raphael Borie, Diane Bouvry, et al.. Contribution of mutations in genes of the surfactant system to idiopathic interstitial pneumonia (IIP). ERS International Congress 2018 abstracts, Sep 2018, Paris, France. pp.OA547, ⟨10.1183/13993003.congress-2018.OA547⟩. ⟨hal-02438688⟩