French cohort RADICO-ILD2 (FIFA): Asymptomatic manifestations in relatives of patients carrying telomere-related gene variants

<bold>Introduction:</bold> Telomere-related gene (TRG) variants may be responsible for pulmonary, hematological, or hepatic diseases. The detection of a variant in a patient allows asymptomatic relatives to know their status regarding this variant. The penetrance and risk factors for pulmonary, hematological, or hepatic diseases in relatives are poorly known. <bold>Method:</bold> The RADICO-FIFA cohort is a French prospective cohort of asymptomatique relatives of TRG mutation carriers, including genetic, phenotypic and environmental data, whatever the presence of the familial variant. <bold>Results:</bold> 101 asymptomatic relatives were included: 59 women (58%) with a mean age of 46 years [33-56]. Genetic analysis results were available for 82 relatives: 52 (63%) carried the familial variant (<italic>TERT</italic>, n=26; <italic>RTEL1</italic>, n=19; <italic>TERC</italic>, n=3; <italic>PARN</italic> = 3; <italic>NHP2</italic>, n=1). Telomere length analysis by FLOW-FISH was available for 36 relatives and 20 (56%) were <10th percentile. At inclusion, the mean FVC was 108% of predicted value [98-119%], and the DLCO was 81% [76-94%]. Among the 66 available chest CT scans, 13 (7 carriers, 18.9%; 6 non-carriers, 20.7%) showed interstitial abnormalities (ground-glass opacities, n=10; traction bronchiectasis, n=4; reticulations, n=13). Only DLCO (78% vs 83%) and KCO (85% vs 93%) were significantly lower in relatives carrying the TRG variant compared to non-carriers. <bold>Conclusion:</bold> Among 101 asymptomatic relatives, only DLCO and KCO differed between those carrying or not the TRG variant, whereas some interstitial abnormalities were found on CT scans in both groups. The scheduled inclusion of 150 relatives, should help identify risk factors for interstitial lung disease in the relatives.

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.oa1064
Primary Topic
Telomeres, Telomerase, and Senescence
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article
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article

French cohort RADICO-ILD2 (FIFA): Asymptomatic manifestations in relatives of patients carrying telomere-related gene variants

Dominique Israël‐Biet, S. Dominique, Aurélie Plessier, Élodie Lainey et al.
Telomeres, Telomerase, and Senescence
article

French cohort RADICO-ILD2 (FIFA): Asymptomatic manifestations in relatives of patients carrying telomere-related gene variants

Dominique Israël‐Biet, S. Dominique, Aurélie Plessier, Élodie Lainey, Laurence Plouvier, Vincent Cottin, S. Marchand‐Adam, A Lassus, Ibrahima Ba, Nadia Nathan, Sonia Guéguen, L Wemeau, I. Nasri, Dominique Valeyre, Claude Guérin, Flore Sicre de Fontbrune, Raphaël Borie, Élodie Blanchard, J.‐C. Dubus, Khalil Bramki, Stéphane Jouneau, Grégoire Prévôt, Caroline Kannengiesser, Hilario Nunes, Claire Andréjak, Philippe Bonniaud, Annick Clément, Bruno Crestani, Jacques Cadranel, Martine Reynaud-Gaudebert
article en

Abstract

<bold>Introduction:</bold> Telomere-related gene (TRG) variants may be responsible for pulmonary, hematological, or hepatic diseases. The detection of a variant in a patient allows asymptomatic relatives to know their status regarding this variant. The penetrance and risk factors for pulmonary, hematological, or hepatic diseases in relatives are poorly known. <bold>Method:</bold> The RADICO-FIFA cohort is a French prospective cohort of asymptomatique relatives of TRG mutation carriers, including genetic, phenotypic and environmental data, whatever the presence of the familial variant. <bold>Results:</bold> 101 asymptomatic relatives were included: 59 women (58%) with a mean age of 46 years [33-56]. Genetic analysis results were available for 82 relatives: 52 (63%) carried the familial variant (<italic>TERT</italic>, n=26; <italic>RTEL1</italic>, n=19; <italic>TERC</italic>, n=3; <italic>PARN</italic> = 3; <italic>NHP2</italic>, n=1). Telomere length analysis by FLOW-FISH was available for 36 relatives and 20 (56%) were <10th percentile. At inclusion, the mean FVC was 108% of predicted value [98-119%], and the DLCO was 81% [76-94%]. Among the 66 available chest CT scans, 13 (7 carriers, 18.9%; 6 non-carriers, 20.7%) showed interstitial abnormalities (ground-glass opacities, n=10; traction bronchiectasis, n=4; reticulations, n=13). Only DLCO (78% vs 83%) and KCO (85% vs 93%) were significantly lower in relatives carrying the TRG variant compared to non-carriers. <bold>Conclusion:</bold> Among 101 asymptomatic relatives, only DLCO and KCO differed between those carrying or not the TRG variant, whereas some interstitial abnormalities were found on CT scans in both groups. The scheduled inclusion of 150 relatives, should help identify risk factors for interstitial lung disease in the relatives.

Université Claude Bernard Lyon 1 (FR), Université de Tours (FR), Inserm (FR), Délégation Paris 7 (FR), Université Paris Cité (FR), Aix-Marseille Université (FR), Hôpital Beaujon (FR), Radiall (France) (FR), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Toulouse (FR), Sorbonne Université (FR), Hôpital Armand-Trousseau (FR), Assistance Publique Hôpitaux de Marseille (FR), Université Sorbonne Paris Nord (FR), Sorbonne Paris Cité (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), Hôpital Européen Georges-Pompidou (FR), Institut de Recherche en Santé, Environnement et Travail (FR), Hôpital Européen (FR), Hôpital Nord (FR), CHU Dijon Bourgogne (FR), Hôpital Pontchaillou (FR), Hôpital Robert-Debré (FR), Hôpital Larrey (FR), Hôpital Avicenne (FR), Hôpitaux Universitaires Henri-Mondor (FR), Hôpital Louis Pradel (FR), Groupe Hospitalier de l'Institut Catholique de Lille (FR), Hôpital Saint-Louis (FR), Hôpital Bichat-Claude-Bernard (FR), Centre Hospitalier Universitaire de Rouen (FR), Physiopathologie et Epidémiologie des Maladies Respiratoires (FR), Centre Hospitalier Universitaire de Rennes (FR), Hôpital Tenon (FR), Centre d'Étude des Pathologies Respiratoires (FR), Maladies génétiques d’expression pédiatrique, Université de Rennes (FR), Université de Rouen Normandie (FR)
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Telomeres, Telomerase, and Senescence
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