Alternative titles; symbols
SNOMEDCT: 765977002; ORPHA: 73271, 98885; DO: 0111057; MONDO: 0013623;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19q13.42 | Bleeding disorder, platelet-type, 11 | 614201 | Autosomal recessive | 3 | GP6 | 605546 |
A number sign (#) is used with this entry because this form of platelet-type bleeding disorder (BDPLT11) can be caused by compound heterozygous mutation in the GP6 gene (605546) on chromosome 19q13.
Platelet-type bleeding disorder-11 (BDPLT11) is an autosomal recessive mild to moderate bleeding disorder caused by defective platelet activation and aggregation in response to collagen (summary by Dumont et al., 2009).
For a discussion of genetic heterogeneity of BDPLT, see 231200.
Dumont et al. (2009) reported a 10-year-old girl with a history of easy bruising since infancy. Laboratory studies showed a prolonged bleeding time and failure of platelet activation and aggregation in response to collagen. Platelet response to ADP, arachidonic acid, and ristocetin was normal. Flow cytometric analysis of platelets showed an incomplete deficiency of glycoprotein VI, and the capacity of the patient's platelets to form thrombi on collagen in flow conditions was strongly impaired, with a 43% decreased surface coverage compared to control. There was also a marked defect in collagen-activated platelet-catalyzed thrombin generation.
Hermans et al. (2009) reported a 31-year-old woman with ecchymoses, epistaxis, several posttraumatic and postsurgery bleeding complications since childhood, and menorrhagia. Laboratory studies showed normal platelet numbers and morphology, but absent platelet activation and aggregation response to collagen. There was also increased adhesion of single platelets, likely due to other receptors. Flow cytometric analysis showed absent GP VI expression on platelets, whereas immunoblot analysis showed reduced but not absent GP VI expression.
The transmission pattern of BDPLT11 in the family reported by Dumont et al. (2009) was consistent with autosomal recessive inheritance.
In a 10-year-old girl with mild platelet-type bleeding disorder-11, Dumont et al. (2009) identified compound heterozygosity for 2 mutations in the GP6 gene (605546.0001-605546.0002). Each parent was heterozygous for 1 of the mutations.
Hermans et al. (2009) identified compound heterozygous GP6 mutations (605546.0003-605546.0004) in a woman with a mild bleeding disorder since childhood.
Dumont, B., Lasne, D., Rothschild, C., Bouabdelli, M., Ollivier, V., Oudin, C., Ajzenberg, N., Grandchamp, B., Jandrot-Perrus, M. Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations. Blood 114: 1900-1903, 2009. [PubMed: 19549989] [Full Text: https://doi.org/10.1182/blood-2009-03-213504]
Hermans, C., Wittevrongel, C., Thys, C., Smethurst, P. A., Van Geet, C., Freson, K. A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder. J. Thromb. Haemost. 7: 1356-1363, 2009. [PubMed: 19552682] [Full Text: https://doi.org/10.1111/j.1538-7836.2009.03520.x]