RT Journal Article SR Electronic T1 Regulator of telomere length 1 (RTEL1)突变与heterogeneou相关联s pulmonary and extra-pulmonary phenotypes JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 1800508 DO 10.1183/13993003.00508-2018 VO 53 IS 2 A1 Borie, Raphael A1 Bouvry, Diane A1 Cottin, Vincent A1 Gauvain, Clement A1 Cazes, Aurélie A1 Debray, Marie-Pierre A1 Cadranel, Jacques A1 Dieude, Philippe A1 Degot, Tristan A1 Dominique, Stephane A1 Gamez, Anne Sophie A1 Jaillet, Madeleine A1 Juge, Pierre-Antoine A1 Londono-Vallejo, Arturo A1 Mailleux, Arnaud A1 Mal, Hervé A1 Boileau, Catherine A1 Menard, Christelle A1 Nunes, Hilario A1 Prevot, Gregoire A1 Quetant, Sebastien A1 Revy, Patrick A1 Traclet, Julie A1 Wemeau-Stervinou, Lidwine A1 Wislez, Marie A1 Kannengiesser, Caroline A1 Crestani, Bruno YR 2019 UL //www.qdcxjkg.com/content/53/2/1800508.abstract AB Regulator of telomere length 1 (RTEL1) mutations have been evidenced in 5–9% of familial pulmonary fibrosis; however, the phenotype of patients with interstitial lung disease (ILD) and RTEL1 mutations is poorly understood.Whole exome sequencing was performed in 252 probands with ILD and we included all patients with ILD and RTEL1 mutation. RTEL1 expression was evaluated by immunochemistry in the lungs of controls, as well as in RTEL1 and telomerase reverse transcriptase (TERT) mutation carriers.We identified 35 subjects from 17 families. Median age at diagnosis of ILD was 53.1 years (range 28.0–80.6). The most frequent pulmonary diagnoses were idiopathic pulmonary fibrosis (n=20, 57%), secondary ILD (n=7, 20%) and unclassifiable fibrosis or interstitial pneumonia with autoimmune features (n=7, 20%). The median transplant-free and overall survival periods were 39.2 months and 45.3 months, respectively. Forced vital capacity at diagnosis was the only factor associated with decreased transplant-free survival. Extra-pulmonary manifestations were less frequent as compared to other telomere-related gene mutation carriers. A systematic analysis of the literature identified 110 patients with ILD and RTEL1 mutations (including this series) and confirmed the heterogeneity of the pulmonary phenotype, the prevalence of non-idiopathic diseases and the low prevalence of extra-pulmonary manifestations.Immunohistochemistry showed that RTEL1 was expressed by bronchial and alveolar epithelial cells, as well as by alveolar macrophages and lymphocytes, but not by fibroblasts.RTEL1 mutations are associated with heterogeneous lung phenotypes with limited and heterogeneous extra-respiratory manifestations http://ow.ly/1Ssr30mCZjx