Submission Details

GATA1 was first reported in relation to GATA1-related X-linked cytopenia in 2000 (Nichols et al, PMID: 10700180), however the disorder was termed familial dyserythropoietic anemia and thrombocytopenia. Subsequently, other terms including X-linked thrombocytopenia with beta-thalassemia, X-linked thrombocytopenia with or without dyserythropoietic anemia, X-linked macrothrombocytopenia, and X-linked anemia with or without neutropenia and/or platelet abnormalities have been used. GATA1-related cytopenia is the accepted term to encompass the heterogeneity of this disorder (Chou et al, 2017, PMID: 20301538). Evidence supporting this gene-disease curation includes case-level data, segregation data, and experimental data. At least 13 unique variants (missense and splicing) have been reported in humans. Variants in this gene have been reported in at least 23 probands in over 20 publications. Variants in this gene segregated with disease in 22 additional family members. The gene disease relationship is supported by animal models (PMID: 8901585; 14656885; 11566888), functional alteration in patient and non-patient cells (PMID: 25621499; 23704091; 12200364; 10700180) and protein interaction studies (PMID: 9230307). Additionally, the GATA1 p.Arg216Trp variant has been associated with three cases of X-linked congenital erythropoietic porphyria, which shares significant phenotypic overlap with GATA1-related cytopenia (PMID:25251786, 17148589). In summary, GATA1 is definitively associated with GATA1-related X-linked cytopenia. This has been repeatedly demonstrated in both the research and the clinical diagnostic settings and has been upheld over time. This curation was approved as a definitive association by the Hemostasis/Thrombosis GCEP on May 27, 2020.