RT Journal Article SR Electronic T1 Regulator of telomere length 1 (RTEL1) mutations are associated with heterogeneous 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 A1 Raphael Borie A1 Diane Bouvry A1 Vincent Cottin A1 Clement Gauvain A1 Aurélie Cazes A1 Marie-Pierre Debray A1 Jacques Cadranel A1 Philippe Dieude A1 Tristan Degot A1 Stephane Dominique A1 Anne Sophie Gamez A1 Madeleine Jaillet A1 Pierre-Antoine Juge A1 Arturo Londono-Vallejo A1 Arnaud Mailleux A1 Hervé Mal A1 Catherine Boileau A1 Christelle Menard A1 Hilario Nunes A1 Gregoire Prevot A1 Sebastien Quetant A1 Patrick Revy A1 Julie Traclet A1 Lidwine Wemeau-Stervinou A1 Marie Wislez A1 Caroline Kannengiesser A1 Bruno Crestani YR 2018 UL http://erj.ersjournals.com/content/early/2018/11/08/13993003.00508-2018.abstract AB RTEL1 mutations have been evidenced in 5–9% of familial pulmonary fibrosis, but the phenotype of patients with interstitial lung disease (ILD) and RTEL1 mutations is poorly known.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 lung of controls, RTEL1 and TERT mutation carriers.We identified 35 subjects, from 17 families. Median age at diagnosis of ILD was 55.2 years [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 IPAF (n=7, 20%). The median transplant-free- and overall-survival were 39.2 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, alveolar macrophages and lymphocytes but not by fibroblast.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Borie reports grants and personal fees from Roche, personal fees from Boerhinger Ingelheim, personal fees from Savapharma, outside the submitted work.Conflict of interest: Dr. Bouvry has nothing to disclose.Conflict of interest: Dr. Cottin reports personal fees from Actelion, personal fees from Boehringer Ingelheim, personal fees from Bayer, personal fees from Gilead, personal fees from GSK, personal fees from MSD, personal fees from Novartis, personal fees from Roche, personal fees from Sanofi, grants from Boehringer Ingelheim, grants from Roche, personal fees from Promedior, personal fees from Celgene, personal fees from Galapagos, outside the submitted work.Conflict of interest: Dr. Gauvain has nothing to disclose.Conflict of interest: Dr. Cazes has nothing to disclose.Conflict of interest: Dr. Debray reports personal fees from Boehringer-Ingelheim, other from Guerbet, from Roche, outside the submitted work.Conflict of interest: Dr. Cadranel has nothing to disclose.Conflict of interest: Dr. Dieude has nothing to disclose.Conflict of interest: Dr. DEGOT reports personal fees and non-financial support from Boerhinger Ingelheim France, personal fees from Roche France, outside the submitted work.Conflict of interest: Dr. DOMINIQUE reports personal fees from ROCHE, personal fees from BOEHRINGER-INGELHEIM, outside the submitted work.Conflict of interest: Dr. Gamez has nothing to disclose.Conflict of interest: Dr. Jaillet has nothing to disclose.Conflict of interest: Dr. Juge has nothing to disclose.Conflict of interest: Dr. Londono-Vallejo has nothing to disclose.Conflict of interest: Dr. Mailleux has nothing to disclose.Conflict of interest: Dr. Mal has nothing to disclose.Conflict of interest: Dr. Boileau has nothing to disclose.Conflict of interest: Dr. Menard has nothing to disclose.Conflict of interest: Dr. Nunes has nothing to disclose.Conflict of interest: Dr. Prevot has nothing to disclose.Conflict of interest: Dr. Quetant has nothing to disclose.Conflict of interest: Dr. Revy has nothing to disclose.Conflict of interest: Dr. Traclet has nothing to disclose.Conflict of interest: Dr. Wislez has nothing to disclose.Conflict of interest: Dr. Kannengiesser has nothing to disclose.Conflict of interest: Dr. Crestani reports grants and personal fees from Boehringer Ingelheim, personal fees from Roche, personal fees from Sanofi, personal fees from Apellis, personal fees from Astra-Zeneca, grants from MedImmune, outside the submitted work.Conflict of interest: Dr. Wemeau Stervinou reports personal fees and non-financial support from Boehringer-Ingelheim, personal fees and non-financial support from Roche, personal fees from Bristol-Myers-Squibb, personal fees from Jansen-Cilag, outside the submitted work.