Clinical and laboratory data from patients with telomerase variants
| Telomerase sequence variant . | Clinical diagnosis . | Telomere length . | Telomerase activity* . |
|---|---|---|---|
| TERC variants | |||
| A48G28 | DC (marrow failure, nail dystrophy) | NA | − |
| Δ52-5528 | DC (hypoplastic myelodysplasia, nail dystrophy) | NA | − |
| Δ79C28 | AA (pancytopenia, leukoplakia) | NA | − |
| Δ28-34 (current study) | AA | 4.0 (7.2) | +++ |
| G58A37 | AA or healthy | ND | +++ |
| TERT variants | |||
| G682D29 | AA | NA | +/− |
| P721R28 | DC | NA | +++ |
| T726M29 | AA (severe) | 4.0 (14.0) | +++ |
| K902N38 | DC (fibrosis of liver and lung, AA, urethral stricture osteoporosis) | See Armanios et al38 | +/− |
| R979W21 | DC (marrow failure) | ≈15.5 (≈16.5) | +++ |
| F1127L21,28 | DC (severe: marrow failure, cerebellar hypoplasia, intrauterine growth retardation, and leukoplakia) | ≈14.0 (≈16.0) | +++ |
| K570N (current study) | AA | 3.1 (7.5) | +/− |
| A279T20,21,28 | AA or healthy | NA | +++ |
| Telomerase sequence variant . | Clinical diagnosis . | Telomere length . | Telomerase activity* . |
|---|---|---|---|
| TERC variants | |||
| A48G28 | DC (marrow failure, nail dystrophy) | NA | − |
| Δ52-5528 | DC (hypoplastic myelodysplasia, nail dystrophy) | NA | − |
| Δ79C28 | AA (pancytopenia, leukoplakia) | NA | − |
| Δ28-34 (current study) | AA | 4.0 (7.2) | +++ |
| G58A37 | AA or healthy | ND | +++ |
| TERT variants | |||
| G682D29 | AA | NA | +/− |
| P721R28 | DC | NA | +++ |
| T726M29 | AA (severe) | 4.0 (14.0) | +++ |
| K902N38 | DC (fibrosis of liver and lung, AA, urethral stricture osteoporosis) | See Armanios et al38 | +/− |
| R979W21 | DC (marrow failure) | ≈15.5 (≈16.5) | +++ |
| F1127L21,28 | DC (severe: marrow failure, cerebellar hypoplasia, intrauterine growth retardation, and leukoplakia) | ≈14.0 (≈16.0) | +++ |
| K570N (current study) | AA | 3.1 (7.5) | +/− |
| A279T20,21,28 | AA or healthy | NA | +++ |
Original descriptions of the indicated sequence variants, associated clinical findings, and telomere length data are indicated by superscript reference citations. Telomere lengths of peripheral blood lymphocytes are expressed in comparison to those of age-matched healthy individuals assayed simultaneously, as reported in the indicated references: +++, within reference range; ++, 2 to 3 kb shorter than the reference range; +, 3 to 6 kb shorter than the reference range.
NA indicates not available; ND, not determined.
*The telomerase activity of each variant was determined in the study by Vulliamy et al21 using reconstituted VA13+hTERT cells and is expressed in comparison to that of wild-type hTERC (+++, 20%-100%; ++, 2%-20%; +, 1%-2%; +/−, > 1%; −, undetectable), based on 2 or 3 independent measurements.