Table 1.
Patient identification [reference] | P2Y12 mutations | Binding sites for 2MeS-ADP | Platelet aggregation induced by ADP ≥ 10 μM | Bleeding time (min) | History of abnormal bleeding |
---|---|---|---|---|---|
VR [26, 34] | p.[Gln98fs] + [Gln98fs] | Severely reduced | Reduced and reversible | 15; 20 | Yes |
ML [28, 36] | p.[Phe240fs] + [?]a | Severely reduced | Reduced and reversible | >20 | Yes |
IG [29, 35] | p.[0] + p.Thr126fsc | Severely reduced | Reduced and reversible | >30 | Yes |
MG [29, 35] | p.[0] + p.Thr126fsc | Severely reduced | Reduced and reversible | 20 | Yes |
OSP-1 [30] | p.[0] + [0]b | NA | Reduced and reversible | >15 | Yes |
?? [31] | p.[Gly12fs] + [Gly12fs] | NA | Reduced and reversible | NA | Yes |
CL [28, 36] | p.[Phe240fs] + [=] | Intermediate | Full and irreversible | NA | No |
GL [29, 35] | p.[0] + [=]c | Intermediate | Full and irreversible | 13 | No |
Patient CL is the daughter of patient ML; patient GL is the son of patient MG who is the sister of patient IG
The upper normal limit of the bleeding time varies between 8 and 10 min in different laboratories
NA not available
aNo mutations were found in one allele of patient ML; however, the findings that the patient’s platelets contained P2Y12 transcripts derived from the mutant allele only and that his daughter (CL) inherited the mutant allele from her father and a normal allele from her mother, suggest that patient ML has an additional, as yet unknown mutation that silences his normal allele (see text for details)
bFailure of expression of the P2Y12 protein (p.[0]) in patient OSP-1 was associated with homozygous single nucleotide substitution in the transduction initiation codon (ATG to AGG)
cp[0] was associated with partial or complete P2Y12 gene deletion in patients IG, MG and GL