GATA1 and JAK3 mutations in children with Down syndrome and TMD or ML-DS
| Patient (group) . | Phenotype at time sample was taken . | Blast count, % (sample origin) . | Mutation in GATA1* . | JAK 3 sequence variant, SNP ref† . |
|---|---|---|---|---|
| 1 (A) | Birth Guthrie sample from child who developed ML-DS | 0 | Exon 2 | rs 3212731 |
| (del 2, pos 202, ins 1, pos 262, subs (A>G), 331) | rs 3212711 | |||
| rs 3212765 | ||||
| 2 (A) | TMD | 50 | Exon 2 | Nil |
| (PB) | (del 132, pos 235) | |||
| 3 (A) | TMD | 55 | Exon 2 | rs 3212731 |
| (aggressive)§ | (BM) | (dup 19, pos 297) | rs 3212711 | |
| rs 2072496 | ||||
| rs 2230589 | ||||
| 4 (A) | TMD | Occasional | Exon 2 | rs 3212765 |
| (PB) | (detected by WAVE)‖ | |||
| 5 (A) | TMD | 25 | Exon 3 | rs 3212731 |
| (PB) | (dup 2, pos 342) | |||
| 6 (A) | TMD | Occasional | Exon 2 | rs 3212731 |
| (PB) | (detected by WAVE)‖ | |||
| 7 (A) | TMD | 76 | Exon 2 | rs 3212711 |
| (aggressive)§ | (BM) | (ins 1, pos 225) | rs 2072496 | |
| 8 (A) | TMD | 25 | Exon 2 | rs 3212731 |
| (PB) | (del 1, pos 266) | |||
| 9 (A) | TMD | 70 | Exon 2 | rs 3212731 |
| (aggressive)§ | (BM) | (del 4, pos 248) | rs 2072496 | |
| 10 (A) | ML-DS | 44 | Exon 2 | rs 3212731 |
| (BM) | (del 23, pos 269) | |||
| 11 (A) | ML-DS | 20 | Exon 2 | rs 3212731 |
| (BM) | (subs (G>A) exon/intron boundary) | |||
| 12 (A) | ML-DS | 20 | Exon 2 | rs 3212731 |
| (BM) | (detected by WAVE)‖ | |||
| 13 (A) | ML-DS | 15 | Exon 2 | rs 3212731 |
| (BM) | (detected by WAVE)‖ | |||
| 14 (A) | ML-DS | 16 | Exon 2 | rs 3212731 |
| (BM) | (subs (C>T) pos 161) | |||
| 15 (A) | ML-DS | 10-15 | Exon 2 | rs 3212731 |
| (BM) | (subs (G>A) exon/intron boundary) | rs 35458530 | ||
| 16 (B) | TMD‡ | 55 | Exon 2 | Nil |
| (PB) | (ins 20, pos 271) | |||
| 17 (B) | TMD‡ | 62 | Exon 2 | Nil |
| (PB) | (ins 1, pos 241) | |||
| 18 (C) | TMD‡ | 68 | Exon 2 | ND |
| (PB) | (del 258-292) | |||
| 19 (C) | TMD‡ | 25 | Exon 2 | ND |
| (PB) | (ins 14, pos 286) | |||
| 20 (C) | TMD‡ | 26 | Exon 2 | ND |
| (PB) | (ins 16, pos 285) | |||
| 21 (C) | ML-DS | 25 | Exon 2 | ND |
| (BM) | (del 22, pos 302) | |||
| 22 (C) | ML-DS | 33 | Exon 2 | ND |
| (BM) | (ins 1, pos 300) | |||
| 23 (C) | ML-DS | 30 | Exon 2 | ND |
| (BM) | (subs (T>G) exon/intron boundary) |
| Patient (group) . | Phenotype at time sample was taken . | Blast count, % (sample origin) . | Mutation in GATA1* . | JAK 3 sequence variant, SNP ref† . |
|---|---|---|---|---|
| 1 (A) | Birth Guthrie sample from child who developed ML-DS | 0 | Exon 2 | rs 3212731 |
| (del 2, pos 202, ins 1, pos 262, subs (A>G), 331) | rs 3212711 | |||
| rs 3212765 | ||||
| 2 (A) | TMD | 50 | Exon 2 | Nil |
| (PB) | (del 132, pos 235) | |||
| 3 (A) | TMD | 55 | Exon 2 | rs 3212731 |
| (aggressive)§ | (BM) | (dup 19, pos 297) | rs 3212711 | |
| rs 2072496 | ||||
| rs 2230589 | ||||
| 4 (A) | TMD | Occasional | Exon 2 | rs 3212765 |
| (PB) | (detected by WAVE)‖ | |||
| 5 (A) | TMD | 25 | Exon 3 | rs 3212731 |
| (PB) | (dup 2, pos 342) | |||
| 6 (A) | TMD | Occasional | Exon 2 | rs 3212731 |
| (PB) | (detected by WAVE)‖ | |||
| 7 (A) | TMD | 76 | Exon 2 | rs 3212711 |
| (aggressive)§ | (BM) | (ins 1, pos 225) | rs 2072496 | |
| 8 (A) | TMD | 25 | Exon 2 | rs 3212731 |
| (PB) | (del 1, pos 266) | |||
| 9 (A) | TMD | 70 | Exon 2 | rs 3212731 |
| (aggressive)§ | (BM) | (del 4, pos 248) | rs 2072496 | |
| 10 (A) | ML-DS | 44 | Exon 2 | rs 3212731 |
| (BM) | (del 23, pos 269) | |||
| 11 (A) | ML-DS | 20 | Exon 2 | rs 3212731 |
| (BM) | (subs (G>A) exon/intron boundary) | |||
| 12 (A) | ML-DS | 20 | Exon 2 | rs 3212731 |
| (BM) | (detected by WAVE)‖ | |||
| 13 (A) | ML-DS | 15 | Exon 2 | rs 3212731 |
| (BM) | (detected by WAVE)‖ | |||
| 14 (A) | ML-DS | 16 | Exon 2 | rs 3212731 |
| (BM) | (subs (C>T) pos 161) | |||
| 15 (A) | ML-DS | 10-15 | Exon 2 | rs 3212731 |
| (BM) | (subs (G>A) exon/intron boundary) | rs 35458530 | ||
| 16 (B) | TMD‡ | 55 | Exon 2 | Nil |
| (PB) | (ins 20, pos 271) | |||
| 17 (B) | TMD‡ | 62 | Exon 2 | Nil |
| (PB) | (ins 1, pos 241) | |||
| 18 (C) | TMD‡ | 68 | Exon 2 | ND |
| (PB) | (del 258-292) | |||
| 19 (C) | TMD‡ | 25 | Exon 2 | ND |
| (PB) | (ins 14, pos 286) | |||
| 20 (C) | TMD‡ | 26 | Exon 2 | ND |
| (PB) | (ins 16, pos 285) | |||
| 21 (C) | ML-DS | 25 | Exon 2 | ND |
| (BM) | (del 22, pos 302) | |||
| 22 (C) | ML-DS | 33 | Exon 2 | ND |
| (BM) | (ins 1, pos 300) | |||
| 23 (C) | ML-DS | 30 | Exon 2 | ND |
| (BM) | (subs (T>G) exon/intron boundary) |
SNP indicates single nucleotide polymorphism; ML-DS, myeloid leukemia of Down syndrome; TMD, transient myeloproliferative disorder; PB, peripheral blood; BM, bone marrow; del, deletion; subs, substitution; ins, insertion; ND, not determined; dup, duplication.
Nucleotide position 1 is taken from Genbank sequence of human GATA1 (NM_002049).
SNP reference number taken from www.ncbi.nlm.nih.gov/SNP/.
Samples previously reported in Mundschau et al.9
Aggressive clinical course (persistent blasts, respiratory and/or liver problems) requiring chemotherapy treatment.
Mutation detected by WAVE only (sensitivity of detection of a mutant clone is >2.5).