BERNARD-SOULIER SYNDROME, TYPE B, INCLUDED
VON WILLEBRAND FACTOR RECEPTOR DEFICIENCY BERNARD-SOULIER SYNDROME, TYPE A1, INCLUDED
BDPLT1
BLEEDING DISORDER, PLATELET-TYPE, 1
BERNARD-SOULIER SYNDROME, TYPE C, INCLUDED
BSS
GLYCOPROTEIN Ib, PLATELET, DEFICIENCY OF
PLATELET GLYCOPROTEIN Ib DEFICIENCY
Bernard-Soulier syndrome is an autosomal recessive bleeding disorder caused by a defect in or deficiency of the platelet membrane von Willebrand factor (VWF; 613160) receptor complex, glycoprotein Ib (GP Ib). GP Ib is composed of 4 subunits encoded ... Bernard-Soulier syndrome is an autosomal recessive bleeding disorder caused by a defect in or deficiency of the platelet membrane von Willebrand factor (VWF; 613160) receptor complex, glycoprotein Ib (GP Ib). GP Ib is composed of 4 subunits encoded by 4 separate genes: GP1BA, GP1BB, GP9, and GP5 (173511). - Genetic Heterogeneity of Platelet-Type Bleeding Disorders Inherited platelet disorders are a heterogeneous group of bleeding disorders affecting platelet number, function, or both. Functional defects can involve platelet receptors, signaling pathways, cytoskeletal proteins, granule contents, activation, or aggregation (review by Cox et al., 2011 and Nurden and Nurden, 2011). Platelet-type bleeding disorders include Bernard-Soulier syndrome (BDPLT1); Glanzmann thrombasthenia (BDPLT2; 273800), caused by mutation in the ITGA2B (607759) or ITGB3 (173470) gene; pseudo-von Willebrand disease (BDPLT3; 177820), caused by mutation in the GP1BA gene (606672); gray platelet syndrome (BDPLT4; 139090), caused by mutation in the NBEAL2 gene (614169); Quebec platelet disorder (BDPLT5; 601709), caused by tandem duplication of the PLAU gene (191840); May-Hegglin anomaly (BDPLT6; 155100), caused by mutation in the MYH9 gene (160775); Scott syndrome (BDPLT7; 262890), caused by mutation in the TMEM16F gene (608663); BDPLT8 (609821), caused by mutation in the P2RY12 gene (600515); BDPLT9 (614200), associated with deficiency of the glycoprotein Ia/IIa receptor (see ITGA2; 192974); glycoprotein IV deficiency (BDPLT10; 608404), caused by mutation in the CD36 gene (173510); BDPLT11 (614201), caused by mutation in the GP6 gene (605546); BDPLT12 (605735), associated with a deficiency of platelet COX1 (176805); susceptibility to BDPLT13 (614009), caused by mutation in the TBXA2R gene (188070); BDPLT14 (614158), associated with deficiency of thromboxane synthetase (TBXAS1; 274180); BDPLT15 (615193), caused by mutation in the ACTN1 gene (102575); and BDPLT16 (187800), caused by mutation in the ITGA2B (607759) or ITGB3 (173470) gene. See reviews by Rao (2003), Cox et al. (2011), and Nurden and Nurden (2011). For a discussion of the genetic heterogeneity of hereditary thrombocytopenia, see THC1 (313900).
Bernard-Soulier syndrome and other platelet disorders have some similar clinical features, including mucosal bleeding, purpuric skin bleeding, epistaxis, and menorrhagia. In BSS, bleeding time is prolonged (in some cases longer than 20 minutes), platelets are large, and there ... Bernard-Soulier syndrome and other platelet disorders have some similar clinical features, including mucosal bleeding, purpuric skin bleeding, epistaxis, and menorrhagia. In BSS, bleeding time is prolonged (in some cases longer than 20 minutes), platelets are large, and there is no platelet aggregation in response to ristocetin or addition of von Willebrand factor. Thrombocytopenia may or may not be present (Lopez et al., 1998). Bernard and Soulier (1948) described a congenital bleeding disorder in patients who had unusually large platelets and a moderate degree of thrombocytopenia. All had a markedly prolonged bleeding time. The same abnormality was described in a family by Kanska et al. (1963). Cullum et al. (1967) described 2 brothers from a consanguineous family of Sicilian origin with a bleeding disorder characterized by thrombocytopenia, abnormally large platelets, prolonged bleeding time, low platelet thromboplastic activity, and normal clotting retraction. All 5 of the brothers' children had abnormal platelet morphology. Multiple other members of the extended family had abnormal platelets without the full bleeding disorder. The authors concluded that the 2 affected brothers were homozygous and the other members with isolated abnormal platelet morphology were heterozygotes. The phospholipid content of platelets was increased. Cullum et al. (1967) suggested that abnormally rapid removal of the bizarre platelets may be responsible for thrombocytopenia. Weiss et al. (1974) studied 2 black first cousins with the disorder.
In a patient with autosomal recessive Bernard-Soulier syndrome, Ware et al. (1990) identified a homozygous nonsense mutation in the GP1BA gene (606672.0001), which encodes the alpha chain of the GP Ib receptor.
By RFLP analysis, Finch ... In a patient with autosomal recessive Bernard-Soulier syndrome, Ware et al. (1990) identified a homozygous nonsense mutation in the GP1BA gene (606672.0001), which encodes the alpha chain of the GP Ib receptor. By RFLP analysis, Finch et al. (1990) ruled out the GP1BA gene as the site of the mutation in a BSS family with 2 affected sibs. The authors suggested that the cause of BSS in this family was due to other genes encoding platelet membrane glycoproteins, including GP1BB, GP IX, and possibly GP V, which may result in failure of assembly and cell surface expression of the von Willebrand factor receptor complex. This suggestion came from the observation that other membrane complexes such as platelet GP IIb-IIIa (273800, 173470) and the T-cell receptor/CD3 complex (186790, 186830, 186740) require coordinate expression of multiple subunits for normal receptor assembly. In a male patient with the velocardiofacial syndrome caused by a deletion in chromosome 22q and symptoms of BSS, Ludlow et al. (1996) identified a mutation in the upstream promoter of the GP1BB gene (138720.0003). Thus, in this patient, BSS resulted from deletion of 1 copy of the gene and mutation in the other copy. In a family with BSS, Wright et al. (1993) identified compound heterozygous mutations in the GP9 gene (173515.0001, 173515.0002). The authors suggested that abnormal GP IX prevented stable assembly of the GP Ib complex. Noda et al. (1995) reported 2 BSS patients: one had a mutation in the GP9 gene and the other had a mutation in the GP1BA gene. They noted that abnormality of a single component of the receptor complex resulted in heterogeneous surface expression of all the components. In 2 Japanese sisters with giant platelets, mild childhood bleeding, and impaired ristocetin aggregation, Kunishima et al. (1997) identified compound heterozygosity for mutations in the GP1BB gene (138720.0001-138720.0002). The authors suggested that the phenotype caused by mutations in the subunits of the GP Ib complex could span the spectrum from a normal phenotype, to isolated giant platelet disorder, to full-blown Bernard-Soulier syndrome.