Summary of mutations at GATA1/exon 2 in DS TMD and AMkL patients
| Patient . | Sex . | FAB . | Gata1 exon 2 mutations . | Analysis of sequence characteristics . | ||
|---|---|---|---|---|---|---|
| Mutation . | Consequence of mutation . | Sequence context . | Notable sequence elements . | |||
| 1 | F | TMD | 114-159del46 | Stop codon after Met84 | ctgggcc[tga…gcc]acc | gcc direct repeat abuts CTGG |
| 2 | M | TMD | 172dup166-171delG | Stop codon after Met84 | –gca(g)ct– | Shares endpoint with 182Dup; direct repeat 175-179 |
| 3 | M | TMD | 221 G>A | Splice mutant | nonCpG | |
| 4 | M | TMD | 174dup159-173insGC | Stop codon after Met84 | (gc)—caccgctgcagctgc– | gctgc direct repeat within duplication |
| 5 | F | TMD | 192dup187-191 | Stop codon after Med84 | tac–tacag– | Direct repeat 205-209; endpoint disrupts TACT |
| 6 | F | M7 | 182dup172-181insGGG | Stop codon before Met84 | ctgg–gcggcactgg–(ggg)cctact | CTGG 5′ end of duplication; shares endpoint with 172Dup; within 2bp of TACT |
| 7 | F | M7 | 114-159del46 | Stop codon after Met84 | ctgggcc[tga…gcc]acc | gcc direct repeat abuts CTGG |
| 8 | M | M7 | 115 G>T | Stop codon before Met84 | nonCpG | |
| 9 | F | M7 | Indel del4-37ins134 | Stop codon before Met84 | atg[gag…cag]agcccct | 3′ endpoint 2 bp from mononculeotide repeats; ins/del disrupts ctgggg/ccccag palindrome |
| 10 | M | M7 | 49 C>T | Stop codon before Met84 | nonCpG; base substitution disrupts palindrome ctgggg/ccccag; disrupted base in bold | |
| 11 | M | M7 | 161-162ins5 | Stop codon before Met84 | cagccac(agtgg)cgctgcagc | Direct repeat |
| 160A>G | G>T is a CpG site | |||||
| 163G>T | Base substitutions surrounding insertion in bold | |||||
| 12 | M | M7 | 149-150insG | Stop codon after Met84 | gcccc(g) agcac | 3′ to GC4 hotspot |
| 13 | M | M7 | 162delCinsTGT | Stop codon after Met84 | cagccacc(tgt)(c)gctgcagc | Direct repeat |
| 14 | M | M7 | 99-100ins4 | Stop codon before Met84 | ggggttttc(nnaa)ttcccct | 3′ to C4T hotspot; within polypyrimidine run; unable to unequivocally determine sequence of 2 bases within insertion |
| 15 | F | M7 | 106-107insT 5A>G | Stop codon before Met84 | ttttcttcccct(t)ttcccctct | Within polypyrimidine run |
| 16 | F | M7 | 184dup84-183 | Stop codon before Met84 | acc—aga…gcc–tact | 100-bp duplication contains CTGG and 6 mononucleotide repeats; TACT endpoint |
| 17 | M | M7 | 2-3insT | No translation from Met1 | at(t)ggag | |
| 18 | M | M7 | 31-32insA | Stop codon before Met84 | ggggtccctgggga(a)cctc | 3′ to 2 TG4 IG heavy-chain hotspots; between palindrome ctgggg/ccccag |
| 143-168del26 | [ctgc…gca]gctgc | Direct repeat | ||||
| 19 | M | M7 | 45dup41-44 | Stop codon before Met84 | agc–ccct–ccccc | Endpoint in mononucleotide run; duplication endpoint at palindrome ctgggg/ccccag |
| Patient . | Sex . | FAB . | Gata1 exon 2 mutations . | Analysis of sequence characteristics . | ||
|---|---|---|---|---|---|---|
| Mutation . | Consequence of mutation . | Sequence context . | Notable sequence elements . | |||
| 1 | F | TMD | 114-159del46 | Stop codon after Met84 | ctgggcc[tga…gcc]acc | gcc direct repeat abuts CTGG |
| 2 | M | TMD | 172dup166-171delG | Stop codon after Met84 | –gca(g)ct– | Shares endpoint with 182Dup; direct repeat 175-179 |
| 3 | M | TMD | 221 G>A | Splice mutant | nonCpG | |
| 4 | M | TMD | 174dup159-173insGC | Stop codon after Met84 | (gc)—caccgctgcagctgc– | gctgc direct repeat within duplication |
| 5 | F | TMD | 192dup187-191 | Stop codon after Med84 | tac–tacag– | Direct repeat 205-209; endpoint disrupts TACT |
| 6 | F | M7 | 182dup172-181insGGG | Stop codon before Met84 | ctgg–gcggcactgg–(ggg)cctact | CTGG 5′ end of duplication; shares endpoint with 172Dup; within 2bp of TACT |
| 7 | F | M7 | 114-159del46 | Stop codon after Met84 | ctgggcc[tga…gcc]acc | gcc direct repeat abuts CTGG |
| 8 | M | M7 | 115 G>T | Stop codon before Met84 | nonCpG | |
| 9 | F | M7 | Indel del4-37ins134 | Stop codon before Met84 | atg[gag…cag]agcccct | 3′ endpoint 2 bp from mononculeotide repeats; ins/del disrupts ctgggg/ccccag palindrome |
| 10 | M | M7 | 49 C>T | Stop codon before Met84 | nonCpG; base substitution disrupts palindrome ctgggg/ccccag; disrupted base in bold | |
| 11 | M | M7 | 161-162ins5 | Stop codon before Met84 | cagccac(agtgg)cgctgcagc | Direct repeat |
| 160A>G | G>T is a CpG site | |||||
| 163G>T | Base substitutions surrounding insertion in bold | |||||
| 12 | M | M7 | 149-150insG | Stop codon after Met84 | gcccc(g) agcac | 3′ to GC4 hotspot |
| 13 | M | M7 | 162delCinsTGT | Stop codon after Met84 | cagccacc(tgt)(c)gctgcagc | Direct repeat |
| 14 | M | M7 | 99-100ins4 | Stop codon before Met84 | ggggttttc(nnaa)ttcccct | 3′ to C4T hotspot; within polypyrimidine run; unable to unequivocally determine sequence of 2 bases within insertion |
| 15 | F | M7 | 106-107insT 5A>G | Stop codon before Met84 | ttttcttcccct(t)ttcccctct | Within polypyrimidine run |
| 16 | F | M7 | 184dup84-183 | Stop codon before Met84 | acc—aga…gcc–tact | 100-bp duplication contains CTGG and 6 mononucleotide repeats; TACT endpoint |
| 17 | M | M7 | 2-3insT | No translation from Met1 | at(t)ggag | |
| 18 | M | M7 | 31-32insA | Stop codon before Met84 | ggggtccctgggga(a)cctc | 3′ to 2 TG4 IG heavy-chain hotspots; between palindrome ctgggg/ccccag |
| 143-168del26 | [ctgc…gca]gctgc | Direct repeat | ||||
| 19 | M | M7 | 45dup41-44 | Stop codon before Met84 | agc–ccct–ccccc | Endpoint in mononucleotide run; duplication endpoint at palindrome ctgggg/ccccag |
Mutations from patient samples were detected as described in ″Methods.″
FAB indicates French-American-British classification; M7, AMkL leukemia; and TMD, transient myeloproliferative disorder. Hyphens indicate duplicated sequence; square brackets indicate deletion endpoints; parentheses enclose inserted or deleted bases; and direct repeats are underlined.
Patients 1 and 7 represent the same person, first presenting with TMD and subsequently presenting with AMkL.