Bernard-Soulier Syndrome via the GP1BB Gene

Bernard-Soulier syndrome (BSS) (OMIM 231200) (also sometimes called giant platelet syndrome) is a bleeding disorder characterized by mild to severe thrombocytopenia with large platelets. Onset is typically in infancy or childhood. Common bleeding problems include purpura, nose bleeds, gingival bleeding, and menorrhagia. BSS is caused by defects in the von Willebrand factor receptor on the platelet cell surface. Platelet-type or pseudo von Willebrand’s disease and benign Mediterranean macrothrombocytopenia are variants of BSS (Balduini et al. Haematologica 87:860-880, 2002). BSS is sometimes misdiagnosed as immune (idiopathic) thrombocytopenic purpura (ITP) (Kunishima et al. Eur J Haematol 76:348-355, 2006).

Bernard-Soulier syndrome (BSS) is an autosomal recessive disorder, although carriers of a single causative variant may have large platelets and mild bleeding problems. Occasionally, the symptoms in carriers are so strong that families display dominant inheritance (Savoia et al. Blood 97:1330-1335, 2001). The von Willebrand factor receptor has four glycoprotein (GP) subunits: GPIbα, GPIbβ, GPIX, and GPV encoded respectively by the GP1BA, GP1BB, GP9, and GP5 genes. Causative variants have been identified to date in all of these genes except GP5. Missense and nonsense variants predominate in cases of BSS, though small and large deletions and regulatory variants have also been reported in all BSS genes (see Lanza 2006). In addition, the Di George/velocardiofacial 22q11.2 deletions often include the GP1BB gene (see Budarf et al. Hum Mol Genet 4:763-766, 1995; and McDonald-McGinn et al.).

This test provides full coverage of all coding exons of the GP1BB gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Sensitivity of this test is unknown. This test will not detect the deleted allele in patients carrying the DiGeorge/velocardiofacial 22q11.2 deletion.