Molecular analysis and telomere length in a family with hTERC mutations. (A) Sequence and PCR analysis of the hTERC gene in patient F17 and family members F43, M44, M14, and F10. The 37A>G substitution is shown in yellow and the nucleotide (nt) 216 to 229 deletions are shown in blue. The presence of both abnormalities is represented by the black symbol. (B) Family pedigree showing inheritance of variant TERC genes (color codes as in panel A). Numbers indicate the ages of the individuals at the time of enrollment into the study. Question marks indicate the absence of clinical information for these individuals. (C) Cartoon illustration of the 2 sequence variants detected in this study (37A>G and 216_229del) relative to the predicted secondary structure of the human telomerase RNA (TERC), based on the phylogenetic analysis of more than 30 different vertebrate TERC RNA sequences (adapted from Chen et al²¹ ). The predicted paired (P1 and P4.1) and junctional regions (J4/4.1) are indicated. (D-E) Telomere-length measurements of the granulocytes (D) and lymphocytes (E) from the individual family members are shown relative to those (curves) of individuals in the general population to have the expected telomere lengths at certain ages (curves are based on a study of 392 control individuals; G. Baerlocher and P.M.L., unpublished data). (F) Diagram showing wild-type and mutant TERC RNA vector sequences used in this study. Note the adenine to guanine substitution at position 37 should still allow for “wobble” base-pairing interaction with its uracil base at position 187. Deletion of nucleotides 216 to 229 in the unpaired region of the RNA is shown by the dashed line. Replacements of primary sequences with complementary sequences are shown in bold.