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Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.

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.

SUBMITTER: Newton CA

PROVIDER: S-EPMC5433348 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.

Newton Chad A CA Batra Kiran K Torrealba Jose J Kozlitina Julia J Glazer Craig S CS Aravena Carlos C Meyer Keith K Raghu Ganesh G Collard Harold R HR Garcia Christine Kim CK

The European respiratory journal 20160818 6

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 di ...[more]

PMID: 27540018

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Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.

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Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.

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