Table 12.2.

Summary of reported human GATA1 mutations and associated phenotypes

DNA nucleotide change	Predicted protein change	Megakaryocyte and platelet phenotype	Red cell phenotype	Other hematologic features	Non-hematologic features	Refs.
Pathogenic variants resulting in GATA1s
c.−21A>G	–	Normal to mild thrombocytosis Dysplastic megakaryocytes	Dyserythropoiesis Mild to severe anemia Macrocytic ↑Hgb F	Occasional neutropenia ML-DS with acquired T21 MDS, AML		[116, 132]
c.2T>C	p.Met1a	Normal to mild thrombocytosis Dysplastic megakaryocytes	Dyserythropoiesis Severe anemia Macrocytic “Clinical DBA”	Progression to MDS Megaloblastic changes ML-DS with acquired T21		[21. 114, 115. 132]
c.3G>A	p.Met1a	Fluctuating thrombocytopenia	Moderate to severe anemia normocytic “Clinical DBA”		Hypertelorism and flat nasal bridge Hepatomegaly	[124]
c.94delG	p.Val32PhefsTer105	Moderate to severe thrombocytopenia Dysplastic megakaryocytes	Mild to severe anemia Normocytic to macrocytic	TAM with acquired T21 Hypercellular, fibrotic marrow	Reported in heterozygous females only	[131]
c.220+2T>C	–	Mild thrombocytosis Dysplastic megakaryocytes	Dyserythropoiesis Moderate anemia Macrocytic “Clinical DBA”			[21]
c.220G>C	p.Val74Leu	Normal or mild thrombocytopenia Dysplastic megakaryocytes Decreased aggregation	Mild to severe anemia Macrocytic	Neutropenia		[19, 20, 113]
Pathogenic variants affecting N-ZF
c.613G>A	p.Val205Met	Mild to severe thrombocytopenia Macrocytosis	Moderate to severe anemia Dyserythropoiesis Fetal hydrops		Cryptorchidism	[53, 150]
c.617A>T	p.Asn206Ile	Severe thrombocytopenia Decreased granules	Mild dyserythropoiesis			[146]
c.622G>A	p.Gly208Arg	Mild to severe thrombocytopenia Macrocytosis	Moderate to severe anemia Dyserythropoiesis		Cryptorchidism Splenomegaly Hepatomegaly Phenotype may improve with age	[144, 147]
c.622_623delGGinsTC	p.Gly208Ser	Severe thrombocytopenia  Hypogranular platelets Macrocytosis Decreased aggregation				[142, 143]
c.647G>A	p.Arg216Gln	Normal to moderate thrombocytopenia Macrocytosis Decreased aggregation, prolonged bleeding time	Mild anemia “β-thalassemia”		Splenomegaly	[117–120, 123,126–128, 141]
c.646C>T	p.Arg216Trp	Moderate thrombocytopenia	Mild anemia “β-thalassemia”		Splenomegaly “X-linked CEP”	[121–123]
c.653A>G	p.Asp218Gly	Moderate to severe thrombocytopenia Macrocytosis Decreased aggregation	Dyserythropoiesis without anemia			[140, 148, 149]
c.652G>T	p.Asp218Tyr	Severe thrombocytopenia Macrocytosis	Severe anemia	Platelets in heterozygous female expressed only wild-type allele		[139]
c.652G>A	p.Asp218Asn	Severe thrombocytopenia Macrocytosis Decreased aggregation, prolonged bleeding time	Dyserythropoiesis without anemia		Splenomegaly	[137, 145]
Pathogenic variants affecting C-ZF
c.788C>T	p.Thr263Met	Moderate thrombocytopenia Dysplastic megakaryocytes	Mild dyserythropoiesis Mild anemia	Leukocytosis (neutrophilia) Hypercellular, brotic marrow	Reported in heterozygous females only	[138]
c.802C>A	p.Leu268Met	Worsening thrombocytopenia with age Decreased aggregation	Anisocytosis, poikilocytosis Progressive macrocytosis with age ↑Hgb F			[146]
c.865C>T	p.His289Tyr	Normal to mild thrombocytopenia Anisocytosis Decreased aggregation, prolonged bleeding time	Dyserythropoiesis Normal to mild anemia			[137]
Pathogenic variants affecting C-TAD
c.871–24C>T	–	Normal to moderate thrombocytopenia Macrocytosis Dysplastic megakaryocytes Decreased aggregation	Dyserythropoiesis Hydrops fetalis, severe infantile anemia Worsening anemia with illness ↑Hgb F	Occasional myeloid dysplasia Progression to aplastic anemia	Cryptorchidism Hypospadias	[112, 133]
c.886A>C	p.Thr296Pro	Moderate thrombocytopenia Macrocytosis Decreased aggregation	Mild dyserythropoiesis Mild anemia ↑Hgb F Lu(a-b-)			[135]
c.919C>T	p.Arg307Cys	Mild thrombocytopenia	Mild dyserythropoiesis Hemolysis “Clinical DBA”	ADA overproduction		[125]
c.920G>A	p.Arg307His	Mild thrombocytopenia Macrocytosis	Variable dyserythropoiesis Hyperchromia Macrocytosis Hemolysis ↑Hgb F Hydrops fetalis, severe infantile anemia Lu(a-b-) “Clinical DBA”	ADA overproduction	Low birth weight Hypospadias Splenomegaly	[125, 134]
c.1240T>C	p.Ter414Arg	Mild thrombocytopenia Macrocytosis	Lu(a-b-)			[136]
Unclassified pathogenic variants
c.515T>C	p.Phe172Ser	Severe thrombocytopenia	Severe anemia	Leukopenia Bone marrow hypoplasia	Mild splenomegaly	[130]

AML acute myeloid leukemia, ADA adenosine deaminase, CEP congenital erythropoietic porphyria, C-TAD carboxy-terminus transactivation domain, C-ZF carboxy-terminus zinc finger, DBA Diamond-Blackfan anemia, Hgb F fetal hemoglobin, Lu Lutheran blood group antigen, MDS myelodysplastic syndrome, ML-DS myeloid leukemia of Down syndrome, N-ZF amino-terminus zinc finger, T21 trisomy 21, TAM transient abnormal myelopoiesis

^aSingle nucleotide mutation that disrupts start codon; an alternative start codon results in GATA1s expression