TERC mutations investigated in this study
. | . | . | . | . | Telomerase activity . | . | . | . | . | . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | . | . | . | . | In vitro . | . | In vivo . | . | . | . | |||||
| Mutation . | Disease . | History of index case at presentation . | Domain . | References* . | This paper, % . | Fu and Collins27 . | This paper, % . | Fu and Collins27 . | Comolli et al37 . | Ly et al29, % . | |||||
| G58A | DC, NSAA, AA, MDS, WT | Various individuals with usually no family history. | Near template | Vulliamy et al30 Wilson et al31 Yamaguchi et al32 Fogarty et al33 | 85 | +++ WT | 100 | +++ 5-fold | — | 100 | |||||
| Normally asymptomatic | |||||||||||||||
| C72G | NSAA | 9-y-old boy with no family history. | Pseudoknot stem P2a. 1 | Vulliamy et al30 | 0 | +++ WT | 5 | ++ 25-fold | — | Low | |||||
| Thrombocytopenia and severe osteoporosis | |||||||||||||||
| 96-7δCT | DC | 40-y-old woman with AD-DC family history. BM failure, mucocutaneous features, osteoporosis, and skin carcinoma | Pseudoknot stem P2b | Vulliamy et al34 | 0 | — | 0 | — | — | — | |||||
| GC107-8AG | DC | 27-y-old woman with AD-DC family history. | Pseudoknot stem P3 | Vulliamy et al8 | 50 | + 25-fold | 5 | + 125-fold | > 100-fold | — | |||||
| Mucocutaneous features | |||||||||||||||
| 110-3δGACT | NSAA | 20-y-old woman with AD-DC family history. | Pseudoknot stem P3 | Vulliamy et al30 | 0 | ++ 5-fold | 0 | — > 125-fold | — | Low | |||||
| BM failure and elphic appearance | |||||||||||||||
| C408G | DC | 12-y-old girl with family history. | CR7 domain stem P8b | Vulliamy et al8 | 100 | +++ WT | 25 | + 125-fold | — | — | |||||
| BM failure, mucocutaneous features, and liver disease | |||||||||||||||
| 378δ → 3′ | DC | 13-y-old boy with AD-DC family history. | Box H/ACA domain | Vulliamy et al8 | 85 | — | 5 | — | — | — | |||||
| BM failure, mucocutaneous features | |||||||||||||||
| G228A | ALT, DC, AA, WT | Patients with AA and African-American control subjects | CR4-5 domain stem P4.1 | Wilson et al31 Yamaguchi et al32 Bryan et al28 | 100 | — | 100 | — | — | — | |||||
. | . | . | . | . | Telomerase activity . | . | . | . | . | . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | . | . | . | . | In vitro . | . | In vivo . | . | . | . | |||||
| Mutation . | Disease . | History of index case at presentation . | Domain . | References* . | This paper, % . | Fu and Collins27 . | This paper, % . | Fu and Collins27 . | Comolli et al37 . | Ly et al29, % . | |||||
| G58A | DC, NSAA, AA, MDS, WT | Various individuals with usually no family history. | Near template | Vulliamy et al30 Wilson et al31 Yamaguchi et al32 Fogarty et al33 | 85 | +++ WT | 100 | +++ 5-fold | — | 100 | |||||
| Normally asymptomatic | |||||||||||||||
| C72G | NSAA | 9-y-old boy with no family history. | Pseudoknot stem P2a. 1 | Vulliamy et al30 | 0 | +++ WT | 5 | ++ 25-fold | — | Low | |||||
| Thrombocytopenia and severe osteoporosis | |||||||||||||||
| 96-7δCT | DC | 40-y-old woman with AD-DC family history. BM failure, mucocutaneous features, osteoporosis, and skin carcinoma | Pseudoknot stem P2b | Vulliamy et al34 | 0 | — | 0 | — | — | — | |||||
| GC107-8AG | DC | 27-y-old woman with AD-DC family history. | Pseudoknot stem P3 | Vulliamy et al8 | 50 | + 25-fold | 5 | + 125-fold | > 100-fold | — | |||||
| Mucocutaneous features | |||||||||||||||
| 110-3δGACT | NSAA | 20-y-old woman with AD-DC family history. | Pseudoknot stem P3 | Vulliamy et al30 | 0 | ++ 5-fold | 0 | — > 125-fold | — | Low | |||||
| BM failure and elphic appearance | |||||||||||||||
| C408G | DC | 12-y-old girl with family history. | CR7 domain stem P8b | Vulliamy et al8 | 100 | +++ WT | 25 | + 125-fold | — | — | |||||
| BM failure, mucocutaneous features, and liver disease | |||||||||||||||
| 378δ → 3′ | DC | 13-y-old boy with AD-DC family history. | Box H/ACA domain | Vulliamy et al8 | 85 | — | 5 | — | — | — | |||||
| BM failure, mucocutaneous features | |||||||||||||||
| G228A | ALT, DC, AA, WT | Patients with AA and African-American control subjects | CR4-5 domain stem P4.1 | Wilson et al31 Yamaguchi et al32 Bryan et al28 | 100 | — | 100 | — | — | — | |||||
Results from recent studies investigating some of the mutants studied here are presented. DC indicates dyskeratosis congenita; NSAA, nonsevere aplastic anemia; AA, aplastic anemia; MDS, myelodysplastic syndrome; WT, wild type/normal. Percentage figures refer to percentage of wild-type activity, figures given as “fold” represent fold decrease over wild type and figures given as n+ represent comparative values in which WT is “++++” in vivo and “+++” in vitro.—indicates not applicable.
References in addition to the current paper.