hTERT variant sequences and hTERC variants.
(A) Schematic depiction of the predicted secondary structure of hTERC as proposed by Chen et al.2 The 11-base template sequence (rectangle) and other structural features are indicated, including the core pseudoknot, CR4-CR5, box H/ACA, and CR7 domains, and the hypervariable paired region. Naturally occurring sequence variations of hTERC are indicated in green for those identified in patients with AA, in red for those found in patients with DC, and in yellow for the G58A variant identified in both healthy individuals and patients. Thick black lines indicate nucleotide deletions. (B) Primary sequences located at the sites of the natural hTERC sequence variations. Nucleotide changes are indicated in boldface, and deletions are dashed or underlined. (C) Linear representation of the hTERT protein with the conserved regions (boxed) located throughout the N-terminal, RT, and C-terminal domains indicated. The disease-associated hTERT sequence variations are indicated in black, whereas the A279T variant that has also been identified in healthy individuals are shown with an asterisk. Note the 2 “DAT” domains (telomerase function that can dissociate from its enzymatic activity) located in both the N- and C-termini of the gene (ie, the N-DAT and C-DAT motifs). (D) Pedigree of a patient with the novel hTERT K570N mutation. The proband (V-11) is indicated with an arrow.
