Genetic and clinical details of persons with GATA2 mutations
| Patient ID . | No. of patients . | Familial or de novo . | GATA2 mutation . | Genomic, cDNA, and protein change . | GATA2 function . | Overall phenotype . | Lymphedema (age onset, y) . | Hematologic abnormalities (age onset, y) with acquired chromosomal anomalies . | Immunodeficiency/infections . | Publications . |
|---|---|---|---|---|---|---|---|---|---|---|
| Patient 1 (FHCRC-97) | 1 female (daughter) | Familial | p.Thr354Met | chr3:g.128 200 744G > A GATA2 c.1061C > T (p.Thr354Met) | DB(−)* | M/A, ID | None | MDS with 5q-clone, aplastic anemia (10) | Recurrent febrile illness, parainfluenza, mycoplasma | Current study |
| Patient 2 (FHCRC-84) | 1 female (daughter) | Familial | p.Thr354Met | chr3:g.128 200 744G > A GATA2 c.1061C > T (p.Thr354Met) | DB(−)* | M/A | None | MDS (14) with 5%-6% monosomy 7, thrombocytopenia (14) | No | Current study |
| Patient 3 (FHCRC-95) | 1 female (mother) | Familial | p.Thr354Met | chr3:g.128 200 744G > A GATA2 c.1061C > T (p.Thr354Met) | DB(−)* | M/A, ID | None | MDS (44) with trisomy 8, leukopenia, anemia, thrombocytopenia (15) | Recurrent infections (pneumonias) as a child | Current study |
| Patient 4 (GC54819) | 1 male | De novo | Contiguous gene deletion encompassing GATA2 gene | chr3:g.127 966 423-136 853 218 (minimum) chr3:g.127 927 712-136 889 323 (maximum) (8.9 Mb 3q21.3-q22.3 deletion) | Null | M/A, ID, DF, NS | None | MDS (dysplastic megakaryopoiesis), leukopenia, anemia, thrombocytopenia, dysplastic megakaryopoiesis | Infections associated with pancytopenia | Current study |
| Patient 5 (French girl) | 1 female | De novo | Contiguous gene deletion encompassing GATA2 gene | 6.9 Mb interstitial 3q21.1-q21.3 deletion (genes ADCY5 - TRH) (∼ chr3:g.123 000 000-129 700 000) | Null | M/A, ID, DF, NS | None | MDS (11) with monosomy 7 on 7/22 metaphases, pancytopenia (11) | Gingivitis and staphylococcal skin infections | Current study, Callier21 |
| Patient 6 (GC42542) | 1 male | De novo | Contiguous gene deletion encompassing GATA2 gene | chr3:g.120 247 726–128 319 968 (minimum) chr3:g.120 154 188-128 324 987 (maximum) (8.2 Mb 3q13.33-q21.3 deletion) | Null | L, M/A, ID, DF, NS | Lymphedema (6.5; bilateral) | MDS/AML (16/29) with trisomy 21 | Recurrent pneumonia and ear infections, H influenza meningitis | Current study, Wildin (submitted) |
| Patient 7 | 1 male | De novo | p.Leu332Thrfs*53 | chr3:g.128 202 727-128 202 728ins GGTC GATA2 c.992_993insGACC (p.Leu332Thrfs*53) | LOF ZF(−) | L, M/A | Lymphedema (birth; bilateral) | Pancytopenia (14) with monosomy 7, MDS (18) with monosomy 7 and trisomy 8, AML (18) | No | Current study |
| Patient 8, kindred 13.I.2 | 1 female (mother) | Familial | p.Met1del290 | chr3:g.128 204 043-128 211 896 GATA2 c.1-200_871 + 527del 2033 bp (p.Met1del290) | Null | L, ID | Lymphedema (unilateral left) | Monocytopenia and B-cell, NK-cell, and T-cell lymphocytopenia | Warts (adulthood), no history of infections disseminated MAC, fungal infections, warts, recurrent pneumonias | Current study, Vinh,27 Hsu7 |
| Patient 9, kindred 13.II.1 | 1 male (son) | Familial | p.Met1del290 | chr3:g.128 204 043-128 211 896 GATA2 c.1-200_871 + 527del 2033 bp (p.Met1del290) | Null | M/A | None | MDS (33) with monosomy 7 on all metaphases, trisomy 8, pancytopenia (33) | Current study, Vinh,27 Hsu7 | |
| Patient 10 | 1 male | De novo | p.? | chr3:g.128 202 701A>C GATA2 c.1017 + 2T>G (p.?) | LOF ZF(−) | M/A, ID | None | MDS (19), monocytopenia (19) | Warts, severe acne | Current study |
| Patient ID . | No. of patients . | Familial or de novo . | GATA2 mutation . | Genomic, cDNA, and protein change . | GATA2 function . | Overall phenotype . | Lymphedema (age onset, y) . | Hematologic abnormalities (age onset, y) with acquired chromosomal anomalies . | Immunodeficiency/infections . | Publications . |
|---|---|---|---|---|---|---|---|---|---|---|
| Patient 1 (FHCRC-97) | 1 female (daughter) | Familial | p.Thr354Met | chr3:g.128 200 744G > A GATA2 c.1061C > T (p.Thr354Met) | DB(−)* | M/A, ID | None | MDS with 5q-clone, aplastic anemia (10) | Recurrent febrile illness, parainfluenza, mycoplasma | Current study |
| Patient 2 (FHCRC-84) | 1 female (daughter) | Familial | p.Thr354Met | chr3:g.128 200 744G > A GATA2 c.1061C > T (p.Thr354Met) | DB(−)* | M/A | None | MDS (14) with 5%-6% monosomy 7, thrombocytopenia (14) | No | Current study |
| Patient 3 (FHCRC-95) | 1 female (mother) | Familial | p.Thr354Met | chr3:g.128 200 744G > A GATA2 c.1061C > T (p.Thr354Met) | DB(−)* | M/A, ID | None | MDS (44) with trisomy 8, leukopenia, anemia, thrombocytopenia (15) | Recurrent infections (pneumonias) as a child | Current study |
| Patient 4 (GC54819) | 1 male | De novo | Contiguous gene deletion encompassing GATA2 gene | chr3:g.127 966 423-136 853 218 (minimum) chr3:g.127 927 712-136 889 323 (maximum) (8.9 Mb 3q21.3-q22.3 deletion) | Null | M/A, ID, DF, NS | None | MDS (dysplastic megakaryopoiesis), leukopenia, anemia, thrombocytopenia, dysplastic megakaryopoiesis | Infections associated with pancytopenia | Current study |
| Patient 5 (French girl) | 1 female | De novo | Contiguous gene deletion encompassing GATA2 gene | 6.9 Mb interstitial 3q21.1-q21.3 deletion (genes ADCY5 - TRH) (∼ chr3:g.123 000 000-129 700 000) | Null | M/A, ID, DF, NS | None | MDS (11) with monosomy 7 on 7/22 metaphases, pancytopenia (11) | Gingivitis and staphylococcal skin infections | Current study, Callier21 |
| Patient 6 (GC42542) | 1 male | De novo | Contiguous gene deletion encompassing GATA2 gene | chr3:g.120 247 726–128 319 968 (minimum) chr3:g.120 154 188-128 324 987 (maximum) (8.2 Mb 3q13.33-q21.3 deletion) | Null | L, M/A, ID, DF, NS | Lymphedema (6.5; bilateral) | MDS/AML (16/29) with trisomy 21 | Recurrent pneumonia and ear infections, H influenza meningitis | Current study, Wildin (submitted) |
| Patient 7 | 1 male | De novo | p.Leu332Thrfs*53 | chr3:g.128 202 727-128 202 728ins GGTC GATA2 c.992_993insGACC (p.Leu332Thrfs*53) | LOF ZF(−) | L, M/A | Lymphedema (birth; bilateral) | Pancytopenia (14) with monosomy 7, MDS (18) with monosomy 7 and trisomy 8, AML (18) | No | Current study |
| Patient 8, kindred 13.I.2 | 1 female (mother) | Familial | p.Met1del290 | chr3:g.128 204 043-128 211 896 GATA2 c.1-200_871 + 527del 2033 bp (p.Met1del290) | Null | L, ID | Lymphedema (unilateral left) | Monocytopenia and B-cell, NK-cell, and T-cell lymphocytopenia | Warts (adulthood), no history of infections disseminated MAC, fungal infections, warts, recurrent pneumonias | Current study, Vinh,27 Hsu7 |
| Patient 9, kindred 13.II.1 | 1 male (son) | Familial | p.Met1del290 | chr3:g.128 204 043-128 211 896 GATA2 c.1-200_871 + 527del 2033 bp (p.Met1del290) | Null | M/A | None | MDS (33) with monosomy 7 on all metaphases, trisomy 8, pancytopenia (33) | Current study, Vinh,27 Hsu7 | |
| Patient 10 | 1 male | De novo | p.? | chr3:g.128 202 701A>C GATA2 c.1017 + 2T>G (p.?) | LOF ZF(−) | M/A, ID | None | MDS (19), monocytopenia (19) | Warts, severe acne | Current study |
Patients 1 to 3 belong to the same family, whereas patients 4 to 6 are unrelated and harbor large heterozygous deletions encompassing the entire GATA2 gene and surrounding genes. Patient 5 has been previously described.21 All mutations numbered from ATG start codon of GATA2 NM_032638.4 and NP_116027.2 (February 2009 GRCh37/hg19).
DB(−) indicates DNA binding disrupted; ZF(−), zinc finger 2 fully or partially deleted; LOF, predicted loss of function; L, lymphedema; M/A, MDS and/or AML; ID, immunodeficiency (DCML or MonoMAC); DF, dysmorphic features; and NS, neurologic symptoms (eg, mental retardation, developmental delay).
Experimentally validated.