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Abstract

Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals. 115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)- specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed. Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year-1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis. Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive.

Original languageEnglish (US)
Pages (from-to)1710-1720
Number of pages11
JournalEuropean Respiratory Journal
Volume48
Issue number6
DOIs
StatePublished - Dec 1 2016

Fingerprint

Telomere
Fibrosis
Lung
Mutation
Interstitial Lung Diseases
Idiopathic Pulmonary Fibrosis
Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Genes
Extrinsic Allergic Alveolitis
Transplants
Connective Tissue Diseases
Telomerase
Vital Capacity
Individuality
Comorbidity
Incidence

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. / Newton, Chad A.; Batra, Kiran; Torrealba, Jose; Kozlitina, Julia; Glazer, Craig S.; Aravena, Carlos; Meyer, Keith; Raghu, Ganesh; Collard, Harold R.; Garcia, Christine Kim.

In: European Respiratory Journal, Vol. 48, No. 6, 01.12.2016, p. 1710-1720.

Research output: Contribution to journalArticle

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AU - Newton, Chad A.

AU - Batra, Kiran

AU - Torrealba, Jose

AU - Kozlitina, Julia

AU - Glazer, Craig S.

AU - Aravena, Carlos

AU - Meyer, Keith

AU - Raghu, Ganesh

AU - Collard, Harold R.

AU - Garcia, Christine Kim

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