{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T12:40:22Z","timestamp":1792240822251,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Objective<\/jats:title>\n \n Interstitial lung diseases (\n ILDs<\/jats:styled-content>\n ) are rare and severe respiratory conditions that may ultimately result in pulmonary fibrosis (\n PF<\/jats:styled-content>\n ). The objective of this study was to present the results of molecular diagnosis of early\u2010onset\n ILD<\/jats:styled-content>\n (from neonates to young adults <\u200950\u2009years) in a reference genetic diagnostic laboratory.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n DNAs<\/jats:styled-content>\n from 699 index cases and 190 relatives were studied over 6\u2009years by Sanger and\/or targeted next generation sequencing of surfactant\u2010related genes and other genes involved in early\u2010onset\n ILD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Pathogenic\/likely pathogenic variants were evidenced for 62 patients (8.9%). The genes most frequently involved were\n \n SFTPA2<\/jats:italic>\n <\/jats:styled-content>\n (13\/62), followed by\n \n ABCA3<\/jats:italic>\n <\/jats:styled-content>\n (12\/62) and\n \n SFTPC<\/jats:italic>\n <\/jats:styled-content>\n (10\/62). Among index cases for whom precise clinical data were available (\n n<\/jats:italic>\n \u2009=\u2009542), indications associated with a high molecular diagnostic yield were pulmonary alveolar proteinosis (61.5%, 8\/13;\n p<\/jats:italic>\n \u2009<\u20090.0007); family history of\n ILD<\/jats:styled-content>\n \/\n PF<\/jats:styled-content>\n and lung cancer (36.8%, 7\/19;\n p<\/jats:italic>\n \u2009=\u20090.0132) and newborns >\u200932\u2009weeks gestation with neonatal respiratory distress (14.8%, 9\/61). The proportion of positive molecular investigations culminated in two age groups over the lifespan: 23.3% (7\/30) in children aged 1 to 10\u2009years, and 18.3% (15\/82) in adults aged 30 to 40\u2009years. Over the 6\u2010year period, 190 relatives were subjected to testing in order to perform segregation studies (\n n<\/jats:italic>\n \u2009=\u2009123) and\/or predictive testing (\n n<\/jats:italic>\n \u2009=\u200979).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This study highlights the specific patient's characteristics associated with a high or low molecular diagnostic yield in clinical practice. Furthermore, it emphasises the importance of establishing a molecular diagnosis in order to provide genetic counselling to the family.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/resp.70132","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T10:37:54Z","timestamp":1759487874000},"page":"53-61","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Molecular Investigation in Early\u2010Onset Interstitial Lung Disease: Results From 699 Unrelated Patients"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2105-1117","authenticated-orcid":false,"given":"Camille","family":"Louvrier","sequence":"first","affiliation":[{"name":"Medical Genetics Department Armand Trousseau Hospital, Sorbonne Universit\u00e9, Assistance Publique \u2013 H\u00f4pitaux de Paris, Molecular Genetics Unit Paris France"},{"name":"Sorbonne Universit\u00e9, Inserm UMR_S933, Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5149-7975","authenticated-orcid":false,"given":"Nadia","family":"Nathan","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm UMR_S933, Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital Paris France"},{"name":"Pediatric Pulmonology Department and Reference Center for Rare Lung Diseases RespiRare Armand Trousseau Hospital, Sorbonne Universit\u00e9, Assistance Publique \u2013 H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5591-0955","authenticated-orcid":false,"given":"Vincent","family":"Cottin","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine National Reference Centre for Rare Pulmonary Diseases, Hospices Civils de Lyon, Universit\u00e9 Lyon 1, UMR754, INRAE, ERN\u2010LUNG Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tifenn","family":"Desroziers","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm UMR_S933, Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Nau","sequence":"additional","affiliation":[{"name":"Medical Genetics Department Armand Trousseau Hospital, Sorbonne Universit\u00e9, Assistance Publique \u2013 H\u00f4pitaux de Paris, Molecular Genetics Unit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohan","family":"Soreze","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm UMR_S933, Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital Paris France"},{"name":"Assistance Publique H\u00f4pitaux de Paris, Intensive Care Unit, Armand Trousseau Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Dastot\u2010Le Moal","sequence":"additional","affiliation":[{"name":"Medical Genetics Department Armand Trousseau Hospital, Sorbonne Universit\u00e9, Assistance Publique \u2013 H\u00f4pitaux de Paris, Molecular Genetics Unit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Reix","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonology Department H\u00f4pital Femme M\u00e8re Enfant, Hospices Civils de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Bouvry","sequence":"additional","affiliation":[{"name":"Service de Pneumologie et Oncologie Thoracique, Centre Constitutif Maladies Pulmonaires Rares de L'adulte, Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Avicenne Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Thumerelle","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonology and Allergy Unit, H\u00f4pital Jeanne de Flandre, University Lille, CHU Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Reynaud\u2010Gaubert","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Lung Transplantation Assistance Publique \u2010 H\u00f4pitaux de Marseille, H\u00f4pital Nord; Aix\u2010Marseille Universit\u00e9 Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Hadchouel","sequence":"additional","affiliation":[{"name":"Assistance Publique \u2013 H\u00f4pitaux de Paris, H\u00f4pital Universitaire Necker\u2010Enfants Malades, Service de Pneumologie P\u00e9diatrique, Centre de R\u00e9f\u00e9rence Pour les Maladies Respiratoires Rares de L'enfant, INSERM U1151 INEM, Universit\u00e9 Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9goire","family":"Pr\u00e9vot","sequence":"additional","affiliation":[{"name":"Service de Pneumologie, H\u00f4pital Larrey Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Effrosyni","family":"Manali","sequence":"additional","affiliation":[{"name":"2nd Pulmonary Department General University Hospital \u201cAttikon\u201d, Medical School, National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Kannengiesser","sequence":"additional","affiliation":[{"name":"Genetics Department Bichat Hospital, AP\u2010HP, Universit\u00e9 Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5338-3883","authenticated-orcid":false,"given":"Ibrahima","family":"Ba","sequence":"additional","affiliation":[{"name":"Genetics Department Bichat Hospital, AP\u2010HP, Universit\u00e9 Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Amselem","sequence":"additional","affiliation":[{"name":"Medical Genetics Department Armand Trousseau Hospital, Sorbonne Universit\u00e9, Assistance Publique \u2013 H\u00f4pitaux de Paris, Molecular Genetics Unit Paris France"},{"name":"Sorbonne Universit\u00e9, Inserm UMR_S933, Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Houdouin","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Universitaire Robert Debr\u00e9, Service de Pneumologie P\u00e9diatrique, Centre de R\u00e9f\u00e9rence Pour les Maladies Respiratoires Rares de l'Enfant, INSERM U1151 INEM, Universit\u00e9 Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9906-0024","authenticated-orcid":false,"given":"Rapha\u00ebl","family":"Borie","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, PHERE, H\u00f4pital Bichat, AP\u2010HP, Service de Pneumologie A, Centre Constitutif du Centre de R\u00e9f\u00e9rence Des Maladies Pulmonaires Rares, FHU APO, LLO Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2178-0846","authenticated-orcid":false,"given":"Marie","family":"Legendre","sequence":"additional","affiliation":[{"name":"Medical Genetics Department Armand Trousseau Hospital, Sorbonne Universit\u00e9, Assistance Publique \u2013 H\u00f4pitaux de Paris, Molecular Genetics Unit Paris France"},{"name":"Sorbonne Universit\u00e9, Inserm UMR_S933, Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"RespiRare and OrphaLung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(22)01052\u20102"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00185114"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1705751"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0251\u20102021"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax\u20102023\u2010221325"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0188\u20102022"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0053\u20102019"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0122\u20102016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0085\u20102020"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00577\u20102022"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.26845"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010019\u20100066\u20103"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0187\u20102019"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20109\u201085"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.03.010"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01554\u20102021"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.14667"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2021.11.008"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202401\u20100238SO"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013660"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200408\u20101104OC"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01809\u20102023"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200600"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.101183"}],"container-title":["Respirology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/resp.70132","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/resp.70132","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/resp.70132","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T10:24:18Z","timestamp":1768386258000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/resp.70132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/resp.70132"],"URL":"https:\/\/doi.org\/10.1111\/resp.70132","archive":["Portico"],"relation":{},"ISSN":["1323-7799","1440-1843"],"issn-type":[{"value":"1323-7799","type":"print"},{"value":"1440-1843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,3]]},"assertion":[{"value":"2025-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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