The Genetics of Interstitial Lung Diseases

Overview

Journal Eur Respir Rev

Specialty Pulmonary Medicine

Date 2019 Sep 27

PMID 31554702

Citations 25

Authors

Raphael Borie

Pierre Le Guen

Mada Ghanem

Camille Taille

Clairelyne Dupin

Philippe Dieude

Caroline Kannengiesser

Bruno Crestani

Affiliations

Soon will be listed here.

Abstract

Interstitial lung diseases (ILDs) are a set of heterogeneous lung diseases characterised by inflammation and, in some cases, fibrosis. These lung conditions lead to dyspnoea, cough, abnormalities in gas exchange, restrictive physiology (characterised by decreased lung volumes), hypoxaemia and, if progressive, respiratory failure. In some cases, ILDs can be caused by systemic diseases or environmental exposures. The ability to treat or cure these ILDs varies based on the subtype and in many cases lung transplantation remains the only curative therapy. There is a growing body of evidence that both common and rare genetic variants contribute to the development and clinical manifestation of many of the ILDs. Here, we review the current understanding of genetic risk and ILD.

Citing Articles

Identification of early genes in the pathophysiology of fibrotic interstitial lung disease in a new model of pulmonary fibrosis.

Hennion N, Bedart C, Vandomber L, Gottrand F, Humez S, Chenivesse C Cell Mol Life Sci. 2025; 82(1):115.

PMID: 40074941 PMC: 11904048. DOI: 10.1007/s00018-025-05620-0.

Diagnosis, screening, and follow-up of patients with familial interstitial lung disease: Results from an international survey.

Moen E, Prior T, Kreuter M, Wuyts W, Molina-Molina M, Wijsenbeek M BMC Pulm Med. 2025; 25(1):59.

PMID: 39901224 PMC: 11792556. DOI: 10.1186/s12890-025-03532-0.

Converging Pathways: A Review of Pulmonary Hypertension in Interstitial Lung Disease.

Lawrence A, Myall K, Mukherjee B, Marino P Life (Basel). 2024; 14(9).

PMID: 39337985 PMC: 11433497. DOI: 10.3390/life14091203.

The Coronavirus Disease 2019 Pandemic and Time to Diagnosis for Childhood Pulmonary Diseases: Outcomes of a Tertiary Care Center.

Akgul Erdal M, Nayir Buyuksahin H, Guzelkas I, Sunman B, Alboga D, Emiralioglu N Turk Arch Pediatr. 2024; 59(4):370-374.

PMID: 39140174 PMC: 11332556. DOI: 10.5152/TurkArchPediatr.2024.23158.

Current Landscape and Future Directions of Patient Education in Adults with Interstitial Lung Disease.

Savvaides T, Demetres M, Aronson K ATS Sch. 2024; 5(1):184-205.

PMID: 38633514 PMC: 11022645. DOI: 10.34197/ats-scholar.2023-0069RE.

References

Borie R, Tabeze L, Thabut G, Nunes H, Cottin V, Marchand-Adam S . Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis. Eur Respir J. 2016; 48(6):1721-1731. DOI: 10.1183/13993003.02115-2015. View

Karimi-Shah B, Chowdhury B . Forced vital capacity in idiopathic pulmonary fibrosis--FDA review of pirfenidone and nintedanib. N Engl J Med. 2015; 372(13):1189-91. DOI: 10.1056/NEJMp1500526. View

Nathan N, Giraud V, Picard C, Nunes H, Dastot-Le Moal F, Copin B . Germline SFTPA1 mutation in familial idiopathic interstitial pneumonia and lung cancer. Hum Mol Genet. 2016; 25(8):1457-67. DOI: 10.1093/hmg/ddw014. View

ODwyer D, Armstrong M, Trujillo G, Cooke G, Keane M, Fallon P . The Toll-like receptor 3 L412F polymorphism and disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2013; 188(12):1442-50. DOI: 10.1164/rccm.201304-0760OC. View

Nir V, Ilivitky A, Hakim F, Yoseph R, Gur M, Mandel H . Pulmonary manifestations of prolidase deficiency. Pediatr Pulmonol. 2016; 51(11):1229-1233. DOI: 10.1002/ppul.23435. View

Lawson W, Loyd J . The genetic approach in pulmonary fibrosis: can it provide clues to this complex disease?. Proc Am Thorac Soc. 2006; 3(4):345-9. PMC: 2658686. DOI: 10.1513/pats.200512-137TK. View

Swaminathan A, Neely M, Frankel C, Kelly F, Petrovski S, Durheim M . Lung Transplant Outcomes in Patients With Pulmonary Fibrosis With Telomere-Related Gene Variants. Chest. 2019; 156(3):477-485. DOI: 10.1016/j.chest.2019.03.030. View

Knight S, Vulliamy T, Copplestone A, Gluckman E, Mason P, Dokal I . Dyskeratosis Congenita (DC) Registry: identification of new features of DC. Br J Haematol. 1999; 103(4):990-6. DOI: 10.1046/j.1365-2141.1998.01103.x. View

Justet A, Thabut G, Manali E, Molina Molina M, Kannengiesser C, Cadranel J . Safety and efficacy of pirfenidone in patients carrying telomerase complex mutation. Eur Respir J. 2018; 51(3). DOI: 10.1183/13993003.01875-2017. View

10.

De Leon A, Cronkhite J, Yilmaz C, Brewington C, Wang R, Xing C . Subclinical lung disease, macrocytosis, and premature graying in kindreds with telomerase (TERT) mutations. Chest. 2011; 140(3):753-763. PMC: 3168855. DOI: 10.1378/chest.10-2865. View

11.

Stanley S, Gable D, Wagner C, Carlile T, Hanumanthu V, Podlevsky J . Loss-of-function mutations in the RNA biogenesis factor NAF1 predispose to pulmonary fibrosis-emphysema. Sci Transl Med. 2016; 8(351):351ra107. PMC: 5351811. DOI: 10.1126/scitranslmed.aaf7837. View

12.

Mechri M, Epaud R, Emond S, Coulomb A, Jaubert F, Tarrant A . Surfactant protein C gene (SFTPC) mutation-associated lung disease: high-resolution computed tomography (HRCT) findings and its relation to histological analysis. Pediatr Pulmonol. 2010; 45(10):1021-9. DOI: 10.1002/ppul.21289. View

13.

Parry E, Alder J, Qi X, Chen J, Armanios M . Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase. Blood. 2011; 117(21):5607-11. PMC: 3110022. DOI: 10.1182/blood-2010-11-322149. View

14.

van Moorsel C, van Oosterhout M, Barlo N, de Jong P, van der Vis J, Ruven H . Surfactant protein C mutations are the basis of a significant portion of adult familial pulmonary fibrosis in a dutch cohort. Am J Respir Crit Care Med. 2010; 182(11):1419-25. DOI: 10.1164/rccm.200906-0953OC. View

15.

Mushiroda T, Wattanapokayakit S, Takahashi A, Nukiwa T, Kudoh S, Ogura T . A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. J Med Genet. 2008; 45(10):654-6. DOI: 10.1136/jmg.2008.057356. View

16.

Schuchman E . The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inherit Metab Dis. 2007; 30(5):654-63. DOI: 10.1007/s10545-007-0632-9. View

17.

Nunes H, Monnet I, Kannengiesser C, Uzunhan Y, Valeyre D, Kambouchner M . Is telomeropathy the explanation for combined pulmonary fibrosis and emphysema syndrome?: report of a family with TERT mutation. Am J Respir Crit Care Med. 2014; 189(6):753-4. DOI: 10.1164/rccm.201309-1724LE. View

18.

Borie R, Kannengiesser C, Hirschi S, Le Pavec J, Mal H, Bergot E . Severe hematologic complications after lung transplantation in patients with telomerase complex mutations. J Heart Lung Transplant. 2015; 34(4):538-46. DOI: 10.1016/j.healun.2014.11.010. View

19.

Alder J, Stanley S, Wagner C, Hamilton M, Hanumanthu V, Armanios M . Exome sequencing identifies mutant TINF2 in a family with pulmonary fibrosis. Chest. 2014; 147(5):1361-1368. PMC: 4420184. DOI: 10.1378/chest.14-1947. View

20.

Hamdan H, Liu H, Li C, Jones C, Lee M, deLemos R . Structure of the human Nkx2.1 gene. Biochim Biophys Acta. 1998; 1396(3):336-48. DOI: 10.1016/s0167-4781(97)00210-8. View