Fig. 2.

Germ-line hTR mutation in an IPF patient with no family history. (A) Secondary structure of hTR. hTR 325 G→T predicts disrupting the integrity of the conserved P5 helix and is thus expected to compromise function. (B) Gel of in vitro reconstituted telomerase with 5-fold dilutions as indicated. Telomerase activity of mutant hTR is compromised as shown by the decreased intensity of the repeat ladder compared with wild type. Quantitation of three independent experiments shown in C indicates that this allele is hypomorphic. Hypomorphic alleles of hTERT and hTR have been previously described in both aplastic anemia and familial IPF patients (5, 6, 18).