Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis

Raphael Borie 1, 2 L. Tabèze 2, 1 Gabriel Thabut 3, 1 Hilario Nunes 4 Vincent Cottin 5, 6 Sylvain Marchand-Adam 7 Grégoire Prevot 8 Abdellatif Tazi 9 Jacques Cadranel 10, 11 Herve Mal 3 Lidwine Wemeau-Stervinou 12 Anne Bergeron Lafaurie 9 Dominique Israel-Biet 13 Clement Picard 14, 15 Martine Reynaud Gaubert 16 Stephane Jouneau 17, 18 Jean-Marc Naccache 10 J. Mankikian 7 Christelle Ménard 19 Jean-François Cordier 20, 21 Dominique Valeyre 22 M. Reocreux 23 Bernard Grandchamp 24 Patrick Revy 25 Caroline Kannengiesser 23 Bruno Crestani 26, 2, 27, 28
Abstract : Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis. We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-Associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival. 237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40-60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046). TERT/TERC DAV were associated with specific clinical and biological features and reduced transplantfree survival. ©ERS 2016.
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Raphael Borie, L. Tabèze, Gabriel Thabut, Hilario Nunes, Vincent Cottin, et al.. Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis. European Respiratory Journal, European Respiratory Society, 2016, 48 (6), pp.1721--1731. ⟨10.1183/13993003.02115-2015⟩. ⟨hal-01467555⟩

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