Fig. 1: A variant in telomerase RNA template alters the canonical telomere sequence.

a Pedigree of the family carrying the TERC r.50 C > A variant. The proband (arrow) was diagnosed with IPF at age 43. Asterisks indicate individuals from which DNA was available. Squares indicate males and circles indicate females. A line through the symbol indicates the individual is deceased. b Apical (upper) and basal (lower) chest CT showing interstitial changes and advanced fibrosis in the proband before lung transplantation. c Graphic showing the location of the patient-derived variant in the template of TR and the resulting telomere sequence. Figure was created with BioRender.com and released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 international license. d Excerpts of telomeric sequences from whole genome sequencing of an individual with no template mutation, the proband, and the proband’s son. Canonical repeats are highlighted in blue, variant TTAGGT repeats are highlighted in yellow, additional non-canonical sequences are in white. e The percentage of TTAGGT repeats in controls, the proband, and the proband’s son. f PNA-FISH for wild-type (red) and variant (green) sequence in a tissue section of the proband’s explanted lung and a control donated lung. Source data for (e) is provided as a Source Data file.