Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis.
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 transplant-free survival.
APHP, Hôpital Bichat, Service de Pneumologie A, DHU FIRE, Centre de compétence des maladies pulmonaires rares, Paris, France.|INSERM, Unité 1152; Université Paris Diderot, Paris, France.
Raphael
R
Borie
APHP, Hôpital Bichat, Service de Pneumologie A, DHU FIRE, Centre de compétence des maladies pulmonaires rares, Paris, France.|INSERM, Unité 1152; Université Paris Diderot, Paris, France.
Laure
L
Tabèze
INSERM, Unité 1152; Université Paris Diderot, Paris, France.|Service de Pneumologie B, APHP, Hôpital Bichat, Paris, France.
Gabriel
G
Thabut
APHP, Service de Pneumologie, Hôpital Avicenne, Bobigny, France.
Hilario
H
Nunes
Service de Pneumologie, Centre national de référence des maladies pulmonaires rares, Hôpital Louis Pradel, Université Claude Bernard Lyon 1, Lyon, France.
Vincent
0000-0002-5591-0955
V
Cottin
Service de Pneumologie, CHRU de Tours, Tours, France.
Sylvain
S
Marchand-Adam
Service de Pneumologie, Hôpital Larrey, Toulouse, France.
Grégoire
G
Prevot
APHP, Hôpital Saint-Louis, Service de Pneumologie, Paris, France.
Abdellatif
A
Tazi
APHP, Service de Pneumologie, Centre de compétence des maladies pulmonaires rares, Hôpital Tenon, Paris, France.
Jacques
J
Cadranel
Service de Pneumologie B, APHP, Hôpital Bichat, Paris, France.
Herve
H
Mal
Service de Pneumologie, Centre de compétence des maladies pulmonaires rares, CHRU de Lille, Lille, France.
Lidwine
L
Wemeau-Stervinou
APHP, Hôpital Saint-Louis, Service de Pneumologie, Paris, France.
Anne
A
Bergeron Lafaurie
APHP, Hôpital Européen Georges Pompidou, Service de Pneumologie, Paris, France.
Dominique
D
Israel-Biet
Service de Pneumologie, Hôpital Foch, Suresnes, France.
Clement
C
Picard
Service de Pneumologie, Hôpital Nord, Marseille, France.
Martine
M
Reynaud Gaubert
Service de Pneumologie, Centre de compétence des maladies pulmonaires rares, Hôpital Pontchaillou; IRSET UMR 1085, université de Rennes 1, Rennes, France.
Stephane
S
Jouneau
APHP, Service de Pneumologie, Centre de compétence des maladies pulmonaires rares, Hôpital Tenon, Paris, France.
Jean-Marc
JM
Naccache
Service de Pneumologie, CHRU de Tours, Tours, France.
Julie
J
Mankikian
Departement de Génétique, APHP, Hôpital Bichat, Paris, France; Université Paris Diderot, Paris, France.
Christelle
C
Ménard
Service de Pneumologie, Centre national de référence des maladies pulmonaires rares, Hôpital Louis Pradel, Université Claude Bernard Lyon 1, Lyon, France.
Jean-François
JF
Cordier
APHP, Service de Pneumologie, Hôpital Avicenne, Bobigny, France.
Dominique
D
Valeyre
Departement de Génétique, APHP, Hôpital Bichat, Paris, France; Université Paris Diderot, Paris, France.
Marion
M
Reocreux
Departement de Génétique, APHP, Hôpital Bichat, Paris, France; Université Paris Diderot, Paris, France.
Bernard
B
Grandchamp
INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France.
Patrick
P
Revy
Departement de Génétique, APHP, Hôpital Bichat, Paris, France; Université Paris Diderot, Paris, France.|Both authors contributed equally to this work.
Caroline
C
Kannengiesser
APHP, Hôpital Bichat, Service de Pneumologie A, DHU FIRE, Centre de compétence des maladies pulmonaires rares, Paris, France bruno.crestani@aphp.fr.|INSERM, Unité 1152; Université Paris Diderot, Paris, France.|Both authors contributed equally to this work.
Bruno
B
Crestani
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics* / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D012313:RNA / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics*; D055815:Young Adult
C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase