Phenotypic variability in GATA1-related thrombocytopenia syndromes
| Mechanism . | Variant . | Thrombocytopenia . | Dyserythropoiesis/ erythroid hypoplasia . | Anemia . | Congenital porphyria . | Globin synthesis imbalance . | Neutropenia . | Ref . |
|---|---|---|---|---|---|---|---|---|
| Impaired binding to FOG1 cofactor | p.V205L | Severe | Dyserythropoiesis | Transfusion dependent | NR | NR | Absent | 69 |
| p.V205M | Severe | Dyserythropoiesis | Severe (fetal hydrops), anemia improved over time | NR | NR | NR | 72 | |
| p.G208S | Severe | Dyserythropoiesis | Absent | NR | NR | Absent | 71 | |
| p.G208R | Severe | Dyserythropoiesis | Transfusion dependent, 1 proband improved with time | NR | NR | Absent | 68,70 | |
| p.D218Y | Severe | Dyserythropoiesis | Transfusion dependent | NR | NR | NR | 73 | |
| p.D218N | Moderate | Absent | Absent | NR | NR | Absent | 75 | |
| p.D218G | Severe | Absent | Absent | NR | NR | Absent | 74 | |
| Impaired binding to DNA | p.R216Q* | Mild-moderate | Dyserythropoiesis | Mild | NR | Present | NR | 22,64–66 |
| p.R216W | Moderate | Dyserythropoiesis | Mild | Present | Present | Absent | 67 | |
| N-TAD truncation variants‡ | c.220G>C† | Moderate | Diagnosed with Diamond-Blackfan anemia: bone marrow erythroid hypoplasia, no other BM abnormalities | Transfusion dependent, robust but transient response to corticosteroids; low reticulocyte counts, modest increase in HgbF | NR | NR | Moderate | 80 |
| Retained intron C-ZF | c.7230 C>T | Intermittent mild-moderate macrothrombocytopenia | Dyserythropoiesis | Severe but improved with time | NR | NR | Absent | 76 |
| Mechanism . | Variant . | Thrombocytopenia . | Dyserythropoiesis/ erythroid hypoplasia . | Anemia . | Congenital porphyria . | Globin synthesis imbalance . | Neutropenia . | Ref . |
|---|---|---|---|---|---|---|---|---|
| Impaired binding to FOG1 cofactor | p.V205L | Severe | Dyserythropoiesis | Transfusion dependent | NR | NR | Absent | 69 |
| p.V205M | Severe | Dyserythropoiesis | Severe (fetal hydrops), anemia improved over time | NR | NR | NR | 72 | |
| p.G208S | Severe | Dyserythropoiesis | Absent | NR | NR | Absent | 71 | |
| p.G208R | Severe | Dyserythropoiesis | Transfusion dependent, 1 proband improved with time | NR | NR | Absent | 68,70 | |
| p.D218Y | Severe | Dyserythropoiesis | Transfusion dependent | NR | NR | NR | 73 | |
| p.D218N | Moderate | Absent | Absent | NR | NR | Absent | 75 | |
| p.D218G | Severe | Absent | Absent | NR | NR | Absent | 74 | |
| Impaired binding to DNA | p.R216Q* | Mild-moderate | Dyserythropoiesis | Mild | NR | Present | NR | 22,64–66 |
| p.R216W | Moderate | Dyserythropoiesis | Mild | Present | Present | Absent | 67 | |
| N-TAD truncation variants‡ | c.220G>C† | Moderate | Diagnosed with Diamond-Blackfan anemia: bone marrow erythroid hypoplasia, no other BM abnormalities | Transfusion dependent, robust but transient response to corticosteroids; low reticulocyte counts, modest increase in HgbF | NR | NR | Moderate | 80 |
| Retained intron C-ZF | c.7230 C>T | Intermittent mild-moderate macrothrombocytopenia | Dyserythropoiesis | Severe but improved with time | NR | NR | Absent | 76 |
N-TAD, N-terminal transactivation domain; C-ZF, C-terminal zinc finger; NR, not reported.
Tubman et al66 refer to the syndrome as “X-linked gray platelet syndrome.”
Two additional studies report patients with the c.220G>C variant as having a phenotype of dysertyrhopoietic anemia, but without thrombocytopenia.77,78
The c.2T>C,79,81 c.-21A>G,162 and c.220delG80 variants also lead to N-TAD truncation variants; patients have DBA-like phenotype but do not have thrombocytopenia.