Pedigrees of 10 probands with personal or family history of telomere-mediated disease. (A) Pedigrees showing males symbolized by squares, females by circles, and deceased individuals with a slash through them. The mutation is listed above each pedigree, and the shaded symbols indicate the diagnoses described in the key above the pedigrees. (B) Telomerase activity assay showing that mutations in hTERT or hTR decrease enzyme activity, as evident by the decreased intensity of the ladder repeat pattern compared with wild-type telomerase (WT). hTERT mutations are referred to by the residue number and the mutant residue. (C) Quantitation of telomerase activity based on at least 3 independent experiments. **P < .01 (2-sided Student t test). (D) Lymphocyte telomere length measured by flow-fluorescence in situ hybridization showing mutation carriers relative to healthy controls. The normal distribution is based on data from 400 controls. Both AA and pulmonary fibrosis probands had telomere length less than the first percentile compared with age-matched controls.