Characteristics of the described patients with congenital P2Y12 defects
| Patient no. . | References . | P2Y12 mutations . | Binding sites for 2MeS-ADP . | Platelet aggregation induced by ADP ≥ 10μM . |
|---|---|---|---|---|
| 1 | 30,43 | p.[Gln98fs]+[Gln98fs] | Severely reduced | Reduced and reversible |
| 2 | 34,45 | p.[Phe240fs]+[?]* | Severely reduced | Reduced and reversible |
| 3, 4 | 26,44 | p.[0]+p.Thr126fs† | Severely reduced | Reduced and reversible |
| 5 | 40 | p.[0]+[0]‡ | Not tested | Reduced and reversible |
| 6 | 41 | p.[Gly12fs]+[Gly12fs] | Not tested | Reduced and reversible |
| 7 | 34,45 | p.[Phe240fs]+[=] | Intermediate | Full and irreversible |
| 8 | 26,44 | p.[0]+[=]† | Intermediate | Full and irreversible |
| 9 | 32 | p.[Arg256Gln]+[Arg265Trp] | Normal | Reduced and reversible |
| 10, 11 | 32 | p.[Arg265Trp]+[=] | Normal | Full and irreversible |
| 12 | 48 | p.[Pro258Thr]+[=] | Not tested | Reduced and reversible |
| 13 | 49 | p.[Lys174Glu]+[=] | Intermediate | Reduced and reversible |
| Patient no. . | References . | P2Y12 mutations . | Binding sites for 2MeS-ADP . | Platelet aggregation induced by ADP ≥ 10μM . |
|---|---|---|---|---|
| 1 | 30,43 | p.[Gln98fs]+[Gln98fs] | Severely reduced | Reduced and reversible |
| 2 | 34,45 | p.[Phe240fs]+[?]* | Severely reduced | Reduced and reversible |
| 3, 4 | 26,44 | p.[0]+p.Thr126fs† | Severely reduced | Reduced and reversible |
| 5 | 40 | p.[0]+[0]‡ | Not tested | Reduced and reversible |
| 6 | 41 | p.[Gly12fs]+[Gly12fs] | Not tested | Reduced and reversible |
| 7 | 34,45 | p.[Phe240fs]+[=] | Intermediate | Full and irreversible |
| 8 | 26,44 | p.[0]+[=]† | Intermediate | Full and irreversible |
| 9 | 32 | p.[Arg256Gln]+[Arg265Trp] | Normal | Reduced and reversible |
| 10, 11 | 32 | p.[Arg265Trp]+[=] | Normal | Full and irreversible |
| 12 | 48 | p.[Pro258Thr]+[=] | Not tested | Reduced and reversible |
| 13 | 49 | p.[Lys174Glu]+[=] | Intermediate | Reduced and reversible |
Patient 7 is the daughter of patient 2; patient 8 is the son of patient 4; patient 10 is the son of patient 9, and patient 11 is the daughter of patient 9.
No mutations were found in one allele of patient 2; however, the findings that the patient's platelets contained P2Y12 transcripts derived from the mutant allele only and that his daughter (patient 7) inherited the mutant allele from her father and a normal allele from her mother, suggest that patient 2 has an additional, as yet unknown, mutation that silences his normal allele.
p[0] was associated with partial or complete P2Y12 gene deletion in patients 3, 4, and 8.
Failure of expression of the P2Y12 protein (p.[0]) in patient 5 was associated with homozygous single nucleotide substitution in the transduction initiation codon (ATG to AGG).