Table 1.
Genotypic and phenotypic characteristics of subjects with platelet dense granule secretion defects
| Family (F)/patient identification* | FLI1 or RUNX1 alteration† | Effect | Platelet count (× 109/L)‡ | Mean platelet volume (fL) | ATP secretion (nmol/1 × 108 platelets)§ |
|---|---|---|---|---|---|
| F1; II.1 | FLI1; c.1009 C>T | p.Arg337Trp | 244 | 10.3 | 0.37 |
| F1; III.1 | FLI1; c.1009 C>T | p.Arg337Trp | 180 | 10.5 | 0.07 |
| F2; II.5 | FLI1; c.1028 A>G | p.Tyr343Cys | 92 | 8.8 | ND|| |
| F2; III.1 | FLI1; c.1028 A>G | p.Tyr343Cys | 117 | 8.6 | ND|| |
| F3.1 | FLI1; c.992-995del | p.Asn331Thrfs*4 | 142 | 11.4 | 0.38 |
| F3.2 | FLI1; c.992-995del | p.Asn331Thrfs*4 | 157 | 11.8 | 0.57 |
| F4.1 | RUNX1; c.508+1 G>T | Splicing | 302 | 7.3 | 0.32 |
| F4.2 | RUNX1; c.508+1 G>T | Splicing | 70 | 7.5 | ND |
| F4.3 | RUNX1; c.508+1 G>T | Splicing | 130 | 7.1 | 0.62 |
| F5 | RUNX1; c.351+1G>T | Splicing | 139 | 8.0 | 0.35 |
| F6.1 | RUNX1; c.317 G>A | p.Trp106Stop | 100 | 8.0 | 0.25 |
| F7 | – | – | 233 | 8.5 | 0.57 |
| F8 | – | – | 190 | 8.5 | ND |
| F9 | – | – | 205 | 8.4 | 0.48 |
| F10 | – | – | 370 | 8.6 | 0.31 |
| F11 | – | – | 225 | NA | 0.63 |
| F12 | – | – | 245 | NA | 0.52 |
| F13 | – | – | 114 | 10.9 | 0.12 |
Heterozygous nucleotide changes present in FLI1 and RUNX1 and their predicted effects on the resulting RNA or protein are shown.
NA, not available; ND, not detectable.
Index cases are indicated in bold font.
Alterations are numbered according to positions in the NM_002017.3 and NM_001754 transcripts for FLI1 and RUNX1, respectively.
Mean platelet counts are shown, the normal reference range is 150 × 109 to 400 × 109 platelets per L, and thrombocytopenia is defined as platelet count <150 × 109 platelets per L.
ATP secreted in response to 100 μM of PAR-1 receptor–specific peptide SFLLRN; fifth percentile in healthy volunteers is 0.82 nmol/1 × 108 platelets.
ATP secretion was measured in response to 1 U/mL of thrombin in the center where these subjects were recruited, against a normal reference range of 0.73 to 1.80 nmol/1 × 108 platelets.