Screening of first-degree relatives of IPF patients with a telomere-related gene mutation

Abstract

Telomere-related gene (TRG) mutations are detected in ±5% of sporadic and 20-30% of familial IPF patients. Up to 30% of asymptomatic relatives of IPF patients have interstitial lung abnormalities on CT. Fibrosis in non-mutation carriers has been described.

We aimed to assess the prevalence of preclinical interstitial lung abnormalities (pILAs: ground-glass or reticular abnormalities, traction bronchiectasis, honeycombing ≥5% of a lung zone) in asymptomatic relatives of IPF patients with a TRG mutation.

First-degree relatives (≥30 years) of IPF patients with a TRG mutation were included. HRCT, pulmonary function test, Sanger Sequencing of TRG mutation and MUC5B promoter polymorphism and telomere length assessment (FLOW-FISH) were performed.

We included 43 relatives (10 families). In 19/43 relatives (44.2%) the TRG mutation was detected. pILAs were observed in 4/24 non-mutation (16.7%) and 4/19 mutation carriers (21.1%). Age (p=0.01) and DLCO%pred (p<0.01) were significantly associated with presence of pILAs; gender, smoking history, FVC%pred, presence of TRG mutation or MUC5B variant and telomere length were not. Of the 4 non-mutation carriers with pILAs, 2 had normal telomere length and 2 did not carry the MUC5B variant.

pILAs were observed in a high proportion of non-mutation carriers. pILAs in non-mutation carriers were not explained by short telomeres or the MUC5B variant. Genetic counseling is therefore difficult.

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