ORPHA: 274; DO: 0111059;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17p13.2 | Bernard-Soulier syndrome, type A2 (dominant) | 153670 | Autosomal dominant | 3 | GP1BA | 606672 |
A number sign (#) is used with this entry because of evidence that an autosomal dominant form of Bernard-Soulier syndrome can be caused by heterozygous mutations in the gene encoding platelet glycoprotein Ib-alpha (GP1BA; 606672) on chromosome 17p.
Autosomal dominant Bernard-Soulier syndrome type A2 (BSSA2) is characterized by chronic macrothrombocytopenia with mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count. When present, clinical findings include excessive ecchymoses, frequent epistaxis, gingival bleeding, prolonged menstrual periods, or prolonged bleeding after tooth extraction (Savoia et al., 2001).
Genetic Heterogeneity of Bernard-Soulier Syndrome
Homozygous or compound heterozygous mutations in the GP1BA gene cause classic autosomal recessive Bernard-Soulier syndrome (BSSA1; 231200).
Miller et al. (1992) reported a 2-generation family in which 5 individuals had a moderate bleeding tendency, thrombocytopenia, and an increased mean platelet volume. The pedigree pattern was consistent with autosomal dominant inheritance.
Savoia et al. (2001) reported 6 Italian families with variable manifestations of a mild bleeding diathesis, incidental discovery of thrombocytopenia, or platelet macrocytosis. Some individuals had no symptoms. Mild bleeding tendencies were manifest as epistaxis, gingival bleeding, menorrhagia, easy bruising, or prolonged bleeding after dental surgery. Members of 3 families had bone marrow examination that showed normal numbers of megakaryocytes.
The transmission pattern of BSSA2 in the family reported by Miller et al. (1992) was consistent with autosomal dominant inheritance.
By linkage analysis of 2 large Italian families with autosomal dominant macrothrombocytopenia, Savoia et al. (2001) found linkage to a region on chromosome 17p, in an interval containing the GP1BA gene (606672).
In a Caucasian family in which 5 members over 2 generations were affected with a mild form of Bernard-Soulier syndrome in an unusual autosomal dominant pattern of inheritance, Miller et al. (1992) identified a heterozygous mutation in the GP1BA gene (L57F; 606672.0004).
In affected individuals of 6 Italian families with autosomal dominant inheritance of large platelets, thrombocytopenia, and mild bleeding tendencies, Savoia et al. (2001) identified a heterozygous mutation in the GP1BA gene (A156V; 606672.0006). The patients were originally thought to have Mediterranean macrothrombocytopenia (see 210250). However, the results of Savoia et al. (2001) indicated that a subset of patients diagnosed with so-called Mediterranean macrothrombocytopenia may actually have a heterozygous type of Bernard-Soulier syndrome.
Miller, J. L., Lyle, V. A., Cunningham, D. Mutation of leucine-57 to phenylalanine in a platelet glycoprotein Ib-alpha leucine tandem repeat occurring in patients with an autosomal dominant variant of Bernard-Soulier disease. Blood 79: 439-446, 1992. [PubMed: 1730088]
Savoia, A., Balduini, C. L., Savino, M., Noris, P., Del Vecchio, M., Perrotta, S., Belletti, S., Poggi, V., Iolascon, A. Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome. Blood 97: 1330-1335, 2001. [PubMed: 11222377] [Full Text: https://doi.org/10.1182/blood.v97.5.1330]