Alternative titles; symbols
ORPHA: 36355; DO: 0060692;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3q25.1 | Bleeding disorder, platelet-type, 8 | 609821 | Autosomal recessive | 3 | P2RY12 | 600515 |
A number sign (#) is used with this entry because of evidence that platelet-type bleeding disorder-8 (BDPLT8) is caused by compound heterozygous mutation in the P2RY12 gene (600515) on chromosome 3q25.
Platelet-type bleeding disorder-8 (BDPLT8) is an autosomal recessive condition characterized by mild to moderate mucocutaneous bleeding and excessive bleeding after surgery or trauma. The defect is due to the inability of ADP to induce platelet aggregation (review by Cattaneo, 2011).
Cattaneo et al. (1992) reported a patient with a congenital defect of platelet function characterized by severe impairment of platelet response to ADP.
Nurden et al. (1995) studied a family in which ADP induced a small and rapidly reversible platelet aggregation even at high doses. This was associated with a markedly reduced binding of ADP to platelets and a failure of ADP to lower the content of cAMP of platelets preincubated with prostaglandin E1. Electron microscopy showed that the ADP-induced aggregates of platelets in the proband were composed of loosely bound shape-changed platelets with few contact points. Thus, this receptor defect had a direct influence on the capacity of platelets to bind to each other in response to ADP. The proband in the family reported by Nurden et al. (1995) was a 61-year-old Caucasian man with a history of episodes of excessive bleeding. The first severe episode occurred at the age of 17 when, after a minor accident, he developed a subretinal hemorrhage that led to the loss of an eye. A second major episode occurred during surgery performed when he was 28 years old. The third episode occurred during middle age when pulmonary bleeding led to hemoptysis. Other affected family members included a father, who died from bleeding after a motor accident, an uncle who died as a result of severe epistaxis, and a sister. The parents of the proband were cousins; there was no information on the mother, who died during the proband's early childhood. The only offspring of the proband appeared normal.
Cattaneo et al. (2003) reported a 60-year-old white man with a lifelong history of easy bruising and excessive posttraumatic and postsurgical blood loss. A daughter and son had never suffered abnormal bleeding episodes.
The transmission pattern of BDPLT8 in the family reported by Cattaneo et al. (2003) was consistent with autosomal recessive inheritance.
In a patient with a bleeding disorder reported by Nurden et al. (1995), Hollopeter et al. (2001) identified a mutation in the P2RY12 gene (600515.0001).
In a patient with a congenital bleeding disorder, Cattaneo et al. (2003) identified compound heterozygosity for 2 mutations in the P2RY12 gene (600515.0002; 600515.0003). His unaffected children were both heterozygous for 1 of the mutations.
Cattaneo, M., Lecchi, A., Randi, A. M., McGregor, J. L., Mannucci, P. M. Identification of a new congenital defect of platelet function characterized by severe impairment of platelet responses to adenosine diphosphate. Blood 80: 2787-2796, 1992. [PubMed: 1333302]
Cattaneo, M., Zighetti, M. L., Lombardi, R., Martinez, C., Lecchi, A., Conley, P. B., Ware, J., Ruggeri, Z. M. Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding. Proc. Nat. Acad. Sci. 100: 1978-1983, 2003. [PubMed: 12578987] [Full Text: https://doi.org/10.1073/pnas.0437879100]
Cattaneo, M. The platelet P2Y12 receptor for adenosine diphosphate: congenital and drug-induced defects. Blood 117: 2102-2112, 2011. [PubMed: 20966167] [Full Text: https://doi.org/10.1182/blood-2010-08-263111]
Hollopeter, G., Jantzen, H.-M., Vincent, D., Li, G., England, L., Ramakrishnan, V., Yang, R.-B., Nurden, P., Nurden, A., Julius, D., Conley, P. B. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 409: 202-206, 2001. [PubMed: 11196645] [Full Text: https://doi.org/10.1038/35051599]
Nurden, P., Savi, P., Heilmann, E., Bihour, C., Herbert, J.-M., Maffrand, J.-P., Nurden, A. An inherited bleeding disorder linked to a defective interaction between ADP and its receptor on platelets: its influence on glycoprotein IIb-IIIa complex function. J. Clin. Invest. 95: 1612-1622, 1995. [PubMed: 7706468] [Full Text: https://doi.org/10.1172/JCI117835]