Characteristics of thrombocytopenic individuals from RUNX1- and GFI1B-mutated families
| Mutation . | Patient . | Sex . | Age . | Bleeding score (F <5, M <3)4 * . | PLT counts, n*109/L (150-450) . | PF4/108 PLTs, μg (0.7-1.5) . | β-TG/106 PLTs, IU (18.6-47.1) . | ADP/108 PLTs, nmol (2.5-5.6) . | ATP/ADP ratio (0.7-1.4) . | Gray PLTs MGG, %† . | Macro PLTs MGG, %† . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| RUNX1 p.Q154fs | I:1 | M | 37 | 6 | 83-111 | 0.4-0.7 | 9.1-20.2 | 1.9-2.1 | N/D | 12 | 0 |
| RUNX1 p.Q154fs | II:1 | F | 6 | N/A | 51-123 | 0.3 | 8.3 | 1.6 | N/D | 6-13 | 0-2 |
| RUNX1 p.Q154fs | II:2 | M | 5 | N/A | 115-139 | 0.3-0.8 | 12.1-19.4 | 1.7-2.7 | 2.1 | 2-6 | 0 |
| RUNX1 p.Q154fs | II:3 | F | 3 | N/A | 85-106 | 1.1 | 14.6 | 1.7 | 2.2 | 14 | 0 |
| RUNX1 TD exons 2-6 affected family member‡ | II:35 § | F5 § | 52 | 3 | 69 | 1.0 | 18.4 | 2.8 | 1.0 | 1 | 0 |
| RUNX1 TD exons 2-6 | II:65 § | M5 § | 53 | 1 | 83-103 | 1.3 | 25.5 | 1.9 | 1.0 | 3 | 0 |
| GFI1B p.Q287* | II:61 § | M1 § | 74 | 251 § | 421 § | 0.41 § | 19.31 § | 4.3 | 1.8 | 39 | 20 |
| GFI1B p.Q287* | II:101 § | M1 § | 65 | 121 § | 44-1161 § | 0.21 § | 5.5-9.81 § | 2.1-3.4 | 2.1 | 27 | 3 |
| GFI1B p.Q287* affected family member‡ | See below|| | M | 42 | 6 | 55-88 | 0.2 | 9.6 | 2.3 | 2.1 | 36 | 5 |
| Mutation . | Patient . | Sex . | Age . | Bleeding score (F <5, M <3)4 * . | PLT counts, n*109/L (150-450) . | PF4/108 PLTs, μg (0.7-1.5) . | β-TG/106 PLTs, IU (18.6-47.1) . | ADP/108 PLTs, nmol (2.5-5.6) . | ATP/ADP ratio (0.7-1.4) . | Gray PLTs MGG, %† . | Macro PLTs MGG, %† . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| RUNX1 p.Q154fs | I:1 | M | 37 | 6 | 83-111 | 0.4-0.7 | 9.1-20.2 | 1.9-2.1 | N/D | 12 | 0 |
| RUNX1 p.Q154fs | II:1 | F | 6 | N/A | 51-123 | 0.3 | 8.3 | 1.6 | N/D | 6-13 | 0-2 |
| RUNX1 p.Q154fs | II:2 | M | 5 | N/A | 115-139 | 0.3-0.8 | 12.1-19.4 | 1.7-2.7 | 2.1 | 2-6 | 0 |
| RUNX1 p.Q154fs | II:3 | F | 3 | N/A | 85-106 | 1.1 | 14.6 | 1.7 | 2.2 | 14 | 0 |
| RUNX1 TD exons 2-6 affected family member‡ | II:35 § | F5 § | 52 | 3 | 69 | 1.0 | 18.4 | 2.8 | 1.0 | 1 | 0 |
| RUNX1 TD exons 2-6 | II:65 § | M5 § | 53 | 1 | 83-103 | 1.3 | 25.5 | 1.9 | 1.0 | 3 | 0 |
| GFI1B p.Q287* | II:61 § | M1 § | 74 | 251 § | 421 § | 0.41 § | 19.31 § | 4.3 | 1.8 | 39 | 20 |
| GFI1B p.Q287* | II:101 § | M1 § | 65 | 121 § | 44-1161 § | 0.21 § | 5.5-9.81 § | 2.1-3.4 | 2.1 | 27 | 3 |
| GFI1B p.Q287* affected family member‡ | See below|| | M | 42 | 6 | 55-88 | 0.2 | 9.6 | 2.3 | 2.1 | 36 | 5 |
All bold values are aberrant. Reference values are indicated between brackets. The family depicted in Figure 1A with the RUNX1 p.Q154fs mutation has not been reported before. See below for further details.
ADP, adenosine diphosphate; ATP, adenosine triphosphate; F, female; M, male; MGG, MGG staining; N/A, not applicable (because cases were too young); N/D, not determined; PLT, platelet; TD, tandem duplication.
Bleeding scores <5 for females (F) and <3 for males (M) indicate bleeding tendency within the normal range.
To determine the percentages of gray platelets (no granules visible by light microscopy, original magnification ×40) and macroplatelets (platelets bigger than normocytic erythrocytes), 100 platelets were scored blindly by 2 technicians.
These individuals were thrombocytopenic, but not tested for the indicated mutation.
Pedigrees from the RUNX1 TD exons 2-6 and GFI1B p.Q287* families were published before (see Figure 1 in Jongmans et al5 and Figure 2 in Monteferrario et al.,1 respectively. As indicated, also other data from GFI1B p.Q287* mutated cases II:6 and II:10 were published before (see supplemental Table 1 in Monteferrario et al1 ).
This case is a son of case II:10 and nephew of II:6, and has platelet CD34 expression (data not shown) but was not included in the previous publication.1