Hematology parameters and ATRX mutations detected to date in patients with ATMDS
Patient number (Oxford ATMDS Registry database no.) . | Patient age in years, sex, clinical diagnosis . | % HbH-containing cells by BCB . | % HbH by electrophoresis . | α/β globin synthesis ratio . | MCV, fL . | ATRX mutation cDNA; predicted protein abnormality if applicable (description) . |
|---|---|---|---|---|---|---|
| 1 (O51) | 60, M, MDS (RA) | 4 | 0 | NA | 69.8 | ND; -14G>A (5′UTR) polymorphism |
| 2 (O65) | 70, M, CMD NOS | 16 | 5.2 | NA | 62 | 20+1G>A (exon 1—intron 1 consensus splice donor site16 ) |
| 3 (O45) | 60, M, MDS (RA) | 35 | 8.7 | 0.11 | 67 | 236C>G, S79X16 |
| 4 (O27) | 76, M, CMD NOS | 50, < 1† | 25, < 1† | 0.09, 1.02† | 65, 78† | 576G>C; L192F |
| 5 (O46) | 70, M, MDS (RA) | 48 | 8.4 | 0.09 | 80.4 | 718T>G; C240G |
| 6 (O54) | 83, M, MDS (RAEB) | 75 | 37.6 | 0.09 | 69.3 | 794G>A; C265Y |
| 7 (O58) | 73, M, MDS (RA) | 16* | 0* | 0.58* | 82* | 2692G>C; D898H‡ |
| 8 (O53) | 76, M, MDS (RAEB) | 25 | NA | NA | 68.4 | Splicing abnormality: exclusion of exon 16, inclusion of segment from intron 16 (see Gibbons et al16 for details) |
| 9 (O61) | 67, M, MDS (RAEB) | 60* | 15* | 0.49* | 66* | Splicing abnormality: inclusion of segment from intron 18 (see Gibbons et al16 for details) |
| 10 (O29) | 86, M, MDS (?RARS) | 14* | 10* | 0.29* | 82* | 5567-3C>G (intron 23—exon 24 consensus splice acceptor site) |
| 11 (O50) | 79, M, MDS (RA) | 10* | 8* | NA | 82.6* | 6083G>C; R2028P |
| 12 (O42) | 71, M, MDS (RA) | 40 | 16.9 | 0.09 | 59.8 | 6884_6885insT; 2293Tfs2319X |
| 13 (O49) | 60, M, MDS (RA) | 25 | 13 | 0.07 | 69.4 | 7014_7017del; N2340fsX2341 |
| 14 (O26) | 61, M, MMM | 5* | 0* | 0.08* | 92* | 7049delT; E2351fsX2353 |
| 15 (O41) | 87, F, ET | 20 | NA | 0.62 | 65 | ND |
| 16 (O43) | 68, M, MDS (RA) | 6.6* | 0* | 0.60* | 88.6* | ND |
| 17 (O69) | 69, M, MDS (RA) | 0.5 | 0 | NA | 72 | ND |
| 18 (O68) | 68, M, MDS NOS | 0.1 | 0 | NA | 72.9 | ND |
Patient number (Oxford ATMDS Registry database no.) . | Patient age in years, sex, clinical diagnosis . | % HbH-containing cells by BCB . | % HbH by electrophoresis . | α/β globin synthesis ratio . | MCV, fL . | ATRX mutation cDNA; predicted protein abnormality if applicable (description) . |
|---|---|---|---|---|---|---|
| 1 (O51) | 60, M, MDS (RA) | 4 | 0 | NA | 69.8 | ND; -14G>A (5′UTR) polymorphism |
| 2 (O65) | 70, M, CMD NOS | 16 | 5.2 | NA | 62 | 20+1G>A (exon 1—intron 1 consensus splice donor site16 ) |
| 3 (O45) | 60, M, MDS (RA) | 35 | 8.7 | 0.11 | 67 | 236C>G, S79X16 |
| 4 (O27) | 76, M, CMD NOS | 50, < 1† | 25, < 1† | 0.09, 1.02† | 65, 78† | 576G>C; L192F |
| 5 (O46) | 70, M, MDS (RA) | 48 | 8.4 | 0.09 | 80.4 | 718T>G; C240G |
| 6 (O54) | 83, M, MDS (RAEB) | 75 | 37.6 | 0.09 | 69.3 | 794G>A; C265Y |
| 7 (O58) | 73, M, MDS (RA) | 16* | 0* | 0.58* | 82* | 2692G>C; D898H‡ |
| 8 (O53) | 76, M, MDS (RAEB) | 25 | NA | NA | 68.4 | Splicing abnormality: exclusion of exon 16, inclusion of segment from intron 16 (see Gibbons et al16 for details) |
| 9 (O61) | 67, M, MDS (RAEB) | 60* | 15* | 0.49* | 66* | Splicing abnormality: inclusion of segment from intron 18 (see Gibbons et al16 for details) |
| 10 (O29) | 86, M, MDS (?RARS) | 14* | 10* | 0.29* | 82* | 5567-3C>G (intron 23—exon 24 consensus splice acceptor site) |
| 11 (O50) | 79, M, MDS (RA) | 10* | 8* | NA | 82.6* | 6083G>C; R2028P |
| 12 (O42) | 71, M, MDS (RA) | 40 | 16.9 | 0.09 | 59.8 | 6884_6885insT; 2293Tfs2319X |
| 13 (O49) | 60, M, MDS (RA) | 25 | 13 | 0.07 | 69.4 | 7014_7017del; N2340fsX2341 |
| 14 (O26) | 61, M, MMM | 5* | 0* | 0.08* | 92* | 7049delT; E2351fsX2353 |
| 15 (O41) | 87, F, ET | 20 | NA | 0.62 | 65 | ND |
| 16 (O43) | 68, M, MDS (RA) | 6.6* | 0* | 0.60* | 88.6* | ND |
| 17 (O69) | 69, M, MDS (RA) | 0.5 | 0 | NA | 72 | ND |
| 18 (O68) | 68, M, MDS NOS | 0.1 | 0 | NA | 72.9 | ND |
Patients no. 2, 3, 8, and 9 were described in Gibbons et al16 ; all other ATRX mutations are newly described here. The precise gDNA mutation responsible for the splicing abnormality detected in cDNA from patients no. 8 and no. 9 is currently unknown.
HbH indicates hemoglobin H; MDS, myelodysplastic syndrome; BCB, brilliant cresyl blue supravital stain; MCV, mean corpuscular volume (normal, 81-99 fL); NA, data not available or assay not performed; ND, no pathologic mutation detected; cDNA, complementary deoxyribonucleic acid; ET, essential thrombocythemia; MMM, myelofibrosis with myeloid metaplasia; CMD NOS, chronic myeloid disorder not otherwise specific; MDS NOS, myelodysplastic syndrome not otherwise specified; RA, refractory anemia; RAEB, refractory anemia with excess blasts; RARS, refractory anemia with ringed sideroblasts (French-American-British Co-operative Group Classification was used to describe MDS subtypes, as most predated the recent reclassification by the World Health Organization); and UTR, untranslated region. ? indicates diagnostic uncertainty.
Patient had been transfused with packed red cells prior to obtaining sample, and HbH level, MCV, and globin synthesis ratio may reflect admixture of patient and donor cells.
Samples were obtained at 2 time points for patient no. 4 (see “Sensitivity of DHPLC for detection of mutations in the ATRX gene”).
Base pair change of uncertain significance, possible polymorphism (see “Comparison of acquired and germ line ATRX mutations”).