Telomerase activity and telomere lengths of wild-type and mutant individuals. (A) In vitro telomerase activity of the mutant TERT proteins in WI-38 VA-13 cells. WI-38 VA-13 cells were transfected with a plasmid expressing the mutant TERT cDNA sequences and a plasmid expressing the WT TERC RNA. Telomerase activity was determined using a Q-PCR–based TRAP assay. Activity is shown in comparison to the activity obtained after transfection with WT TERT cDNA (=1.0). Telomerase activity in 293T cells served as a positive control. (B) In vitro telomerase activity of 2 mutants or 1 mutant and WT TERT proteins in WI-38 VA-13 cells. WI-38 VA-13 cells were cotransfected with 2 plasmids expressing 2 different mutants, or 1 mutant and the WT TERT cDNA sequences. Equal amounts of plasmid expressing the TERC RNA were cotransfected in all experiments. Activity is shown in comparison to the activity obtained after the transfection of equal amounts of the WT TERT (=1.0). Experiments were performed 4 times and cotransfection experiments twice. The comparison of telomerase activity between the variants was performed by ANOVA analysis followed by post hoc test. Statistically significant reduction of telomerase activity (P < .05) is indicated with . Error bars represent SD. (C) Telomere lengths measured in PBMN cells. Lines represent percentiles (1%-99%) of telomere length measured in 234 healthy individuals between the ages of 0.3 to 94 years old. The telomere lengths of family 199 are represented as ● and those of 284 as △ and ▲. Filled symbols indicate those with mutations (see text and Figure 1), empty symbols indicate family members carrying 2 wild-type alleles.