Telomere-related mutations in a prospective CTD-ILD cohort

<bold>Background:</bold> Several genetic variants are known to contribute to pulmonary fibrosis risk, but little is known about their frequency in connective tissue disease-associated interstitial lung disease (CTD-ILD). <bold>Objective:</bold> Assess frequency and clinical significance of telomere-related mutations in a prospective CTD-ILD cohort. <bold>Method:</bold> We conducted exome sequencing and analysis of 26 familial pulmonary fibrosis genes of 98 CTD-ILD patients from Oslo University Hospital. All patients were followed prospectively over 12 months with clinical assessments, lung function tests, biochemistry and HRCT findings. <bold>Result:</bold> Among the 98 patients, we identified four individuals (4 %) with pathogenic or likely pathogenic variants in TERT, PARN and RTEL1 (two variants), and additionally two patients with variants of uncertain significance (VUS). All 4 patients with pathogenic or likely pathogenic variants had hematological abnormalities, but no other specific clinical features could be identified. <bold>Conclusion:</bold> In this prospective and well-characterized CTD-ILD cohort, telomere-related mutations were less frequent than previously reported, but possibly associated with more complex phenotypes. Importantly, to the best of our knowledge, our study is the first to investigate such mutations in a strictly defined CTD-ILD cohort. Our findings underscore the need for exploring the prognostic significance of telomere-related mutations in larger and longer-term cohorts. <fig><object-id>erj;64/suppl_68/PA4262/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>