Table 1.
Complete blood count and bone marrow characteristics of individuals with germ line DDX41 mutations
| Panel in Figure 1 | Pedigree | Individual | DDX41 mutation† | Age at time of CBC (y) | Status of HM at time of CBC | WBC (K/μL) | Hgb (g/dL) | MCV (fL) | ANC (K/μL) | Plt (K/μL) | HM diagnosis | BM cellularity | BM dysplasia | Karyotype |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Malignancy | ||||||||||||||
| A | 33755 | III.1 | p.D140Gfs*2 | 54 | At dx | 1.6 | 13.3 | 108.0 | 0.5 | 128 | AML (M6) | 20% | Erythroid dysplasia | 46,XY[20] |
| B | 235 | II.2 | p.D140Gfs*2 | 69 | At dx | 2.2 | — | — | — | 89 | AML | 15% | No | 46,XX[20] |
| C | 277 | II.1 | p.D140Gfs*2 | 73 | At dx | 1.5 | 8.5 | 112.0 | 0.3 | 62 | AML | 20%-40%; CD5+, CD19+ lymphoid aggregates | Erythroid dysplasia | 46,XY,del(5)(q31.1q34)[6]/ 46,idem,inv(1)(q21q31)[10]/46,XY[4] |
| D | 154 | II.2 | c.435-2_435-1delAGinsCA | 67 | At dx | 3.3 | 12.5 | 92.3 | 1.9 | 102 | MDS (RAEB-2) | 15%-25% | Erythroid dysplasia, rare dysplastic megakaryocyte or myeloid precursor | 46,XY[20] |
| E | 20432 | II.3 | p.M1I‡ | 58 | At dx1 | 0.7 | 8.7 | 103.0 | 0.1 | 34 | AML (M6) | Normal | Erythroid and megakaryocytic dysplasia | 46,XY |
| E | 20432 | II.3 | p.M1I‡ | 59 | At dx2 | 1.2 | 6.5 | 104.0 | 0.08 | 27 | AML now with NHL involvement | Hypocellular; lymphoid aggregates consistent with NHL | Erythroid and megakaryocytic dysplasia | — |
| E | 20432 | III.1 | p.M1I | 33 | 1 mo after dx | 34.7 | 11.0 | 92.0 | 25.3 | 333 | CML | Hypercellular | No | 46,XX, t(9;22)(q34;q11)[16]/ 46,XX[2] |
| F | 236 | II.3 | p.M1I‡ | 72 | At dx | 2.6 | 10.6 | 107.2 | 0.7 | 41 | MDS (RAEB-2) | 5%-10% | Megakaryocytic dysplasia | 46,XX[20] |
| F | 236 | II.6 | p.M1I | 74 | At dx | 4.1 | 13.3 | — | 1.4 | 66 | AML | 15%-20% | No | 47,XY,+8[2]/46,XY[18] |
| G | 31379 | III.1 | p.R525H | 56 | At dx | 3.2 | 15.0 | 102.0 | 1.7 | 171 | MDS (RAEB-2) | Hypercellular | Trilineage dysplasia | 46,XX |
| G | 31379 | III.1 | p.R525H | 58 | 24 mo after dx | 3.2 | 14.0 | 99.0 | 1.6 | 179 | MDS (RAEB-2) | — | Trilineage dysplasia | 46,XX [20] |
| G | 31379 | III.6 | p.R525H | 55 | At dx | 0.4 | 12.0 | 113.1 | 0.2 | 47 | AML | 20% | No | — |
| H | 230 | II.5 | p.G530D‡ | 53 | At dx | — | — | — | — | — | AML | — | — | — |
| H | 230 | II.6 | p.G530D‡ | 44 | At dx | — | — | — | — | — | AML | — | — | — |
| H | 230 | III.6 | p.G530D | 50 | At dx | 2.4 | 14.0 | 99.7 | 0.6 | 151 | AML | 30% | No | 46,XY[20] |
| I | 25476 | III.1 | p.R164W | 55 | At dx | 9.3 | 15.2 | 88.0 | — | 320 | FL (grade 2) | Hypercellular; FL involvement | Mild erythroid dysplasia | 46,XY[15] |
| I | 25476 | III.4 | p.R164W | 48 | At dx | 7.6 | 13.1 | 88.7 | — | 347 | FL (grade 1) | Hypercellular: FL involvement | No | — |
| I | 25476 | III.7 | p.R164W | 55 | At dx | 7.1 | 12.5 | 88.0 | 3.3 | 223 | FL (grade 1) | 30%-50% | No | 46,XX[20] |
| S5§ | 127 | II.11 | p.D140Gfs*2 | 73 | At dx | 3.6 | 12.5 | 97.9 | — | 135 | AML (M6) | 15%-20% | Erythroid dysplasia | 46,XY[20] |
| S5§ | 127 | III.7 | p.D140Gfs*2 | 56 | At dx | 1.1 | 10.0 | 95.8 | 0.2 | 27 | AML | 20% | No | 46,XY,del(20)(q11.21-q13.33)[4]/46,XY[14] |
| Premalignancy | ||||||||||||||
| A | 33755 | III.1 | p.D140Gfs*2 | 54 | 4 mo before AML dx | 2.3 | 15.0 | 102.0 | 1.0 | 145 | ||||
| A | 33755 | III.1 | p.D140Gfs*2 | 52 | 29 mo before AML dx | 5.2 | 15.7 | 92.0 | 3.5 | 225 | ||||
| D | 154 | II.1 | c.435-2_435-1delAGinsCA | 75 | NA | 8.7 | 12.3 | 90.0 | 5.6 | 184 | ||||
| E | 20432 | III.1 | p.M1I | 30 | 29 mo before CML dx | 7.9 | 12.7 | 87.0 | 6.2 | 274 | ||||
| F | 236 | II.6 | p.M1I | 72 | 23 mo before AML dx | — | — | — | — | 123 | ||||
| F | 236 | II.6 | p.M1I | 73 | 15 mo before AML dx | 3.5 | 13.3 | — | 1.5 | 72 | ||||
| H | 230 | III.5 | p.G530D | 63 | NA | 5.7 | 14.2 | 91.3 | 3.6 | 336 | ||||
| H | 230 | III.6 | p.G530D | 50 | 2 mo before AML dx | 2.8 | 14.6 | 97.8 | 1.0 | 185 | ||||
| H | 230 | III.8 | p.G530D | 59 | NA | 3.1 | 12.8 | 100.5 | 1.4 | 180 | ||||
| S5§ | 127 | II.6 | p.D140Gfs*2 | 87 | NA | 8.4 | 14.2 | 94.0 | 4.4 | 296 | ||||
| S5§ | 127 | II.8 | p.D140Gfs*2 | 85 | NA | 5.8 | 12.9 | 93.7 | 3.7 | 126 | None | 20%-30% | No | 46,XY[19] |
| S5§ | 127 | II.10 | p.D140Gfs*2 | 79 | NA | 10.0 | 13.0 | 96.0 | — | 213 | ||||
| S5§ | 127 | II.12 | p.D140Gfs*2 | 75 | NA | 7.5 | 13.9 | 103.0 | 3.7 | 354 | ||||
| S5§ | 127 | III.1 | p.D140Gfs*2 | 60 | NA | 5.1 | 14.6 | 89.6 | — | 189 | ||||
| S5§ | 127 | III.3 | p.D140Gfs*2 | 65 | NA | 9.4 | 15.0 | 90.0 | — | 231 | ||||
| S5§ | 127 | III.8 | p.D140Gfs*2 | 57 | NA | 6.0 | 16.7 | 89.2 | 3.8 | 187 | ||||
| S5§ | 127 | IV.2 | p.D140Gfs*2 | 35 | NA | 8.4 | 14.4 | 91.3 | — | 348 | ||||
| S5§ | 127 | IV.3 | p.D140Gfs*2 | 20 | NA | 4.5 | 13.3 | 94.2 | 2.6 | 165 | ||||
| Controls | ||||||||||||||
| C | 277 | III.2 | WT | 41 | NA | 8.3 | 14.0 | 89.3 | 5.7 | 213 | ||||
| C | 277 | III.3 | WT | 38 | NA | 11.3 | 15.1 | 98.0 | — | 202 | ||||
| H | 230 | III.7 | WT | 65 | NA | 6.2 | 14.2 | 94.4 | — | 262 | ||||
| S5§ | 127 | III.5 | WT | 62 | NA | 4.9 | 13.3 | 88.3 | 2.8 | 213 | ||||
| S5§ | 127 | III.10 | WT | 46 | NA | 6.8 | 13.5 | 90.0 | 4.4 | 313 | ||||
Dash indicates that information is not available.
AML, acute myeloid leukemia; ANC, absolute neutrophil count; BM, bone marrow; CBC, complete blood count; CML, chronic myeloid leukemia; dx, diagnosis; FL, follicular lymphoma; Hgb, hemoglobin; HM, hematologic malignancy; M6, French-American-British subtype; MCV, mean corpuscular volume; MDS, myelodysplastic syndrome; NA, not applicable; NHL, non-Hodgkin lymphoma; Plt, platelet count; RAEB-2, refractory anemia with excess blasts 2; WBC, white blood cell count, WT, wild type.
†
Numbering for all complementary DNAs and proteins refers to NM_016222.2 and NP_057306.2.
‡
Obligate carrier.
§
Pedigree 127 is included in supplemental Figure 5.