Genetic Abnormalities of Bernard-Soulier Syndrome

Abstract

Bernard-Soulier Syndrome (BSS) is an autosomal recessive bleeding disorder due to quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V complex, the platelet receptor for von Willebrand factor. BSS is characterized by giant platelets, thrombocytopenia, and prolonged bleeding time, and the hallmark of this disorder is the absence of ristocetin-induced platelet agglutination. In the last 10 years, the molecular and genetic bases of many GPIb/IX/V defects have been elucidated, providing a better understanding of primary hemostasis and structure-function relations of the complex. Thus far, more than 30 mutations of the GPIbalpha, GPIbbeta, or GPIX genes have been described in BSS. Recent studies also have shown that the phenotypes caused by mutations in the subunits of the GPIb/IX/V span a wide spectrum, from the normal phenotype, to isolated giant platelet disorders/macrothrombocytopenia, to full-blown BSS and platelet-type von Willebrand disease. Although recent progress in molecular biology has clarified the genotype-phenotype relationships of the GPIb/IX/V disorders, a close examination of platelet morphology on blood smears is still indispensable for a proper diagnosis. In this review, we summarize recent advances in the molecular basis of BSS with special emphasis on giant platelets and the genetic characteristics of Japanese BSS.

Compound heterozygosity for a novel nine-nucleotide deletion and the Asn45Ser missense mutation in the glycoprotein IX gene in a patient with Bernard-Soulier syndrome

“…They are simple in structure and intron-free except that for GPIb , which contains a short intron in the coding region. To date, most of the mutations identified in BSS patients have been found in the GPIb gene, but some are also found in the GPIb and GPIX genes [4]. None have been found in the GPV gene.…”

A Case Report of Bernard-Soulier Syndrome in Differential Diagnosis of Immune Thrombocytopenic Purpura.

“…They had platelet counts from 22 to 178 × 10 9 /L. The mean value of MPV was 12.6 fL, with a range from 10.4 to 17.2 fL [92].…”

“…Mutation of the glycoprotein (GP) Ib/IX complex associated with Bernard-Soulier Syndrome (See Table 5) [92] Idiopathic thrombocytopenicpurpura, leukemia should be included in the differential diagnosis of patients with Bernard-Soulier syndrome. Patients with idiopathic thrombocytopenic may have detectable antiplatelet antibodies.…”

Management of Inherited Bleeding Disorders in Pregnancy

“…More than 30 genetic mutations have been identified, determining various severities of bleeding. 205 Bleeding often starts in childhood with oral bleeding and epistaxis, but patients may be first diagnosed in pregnancy. Menorrhagia is common and can be challenging to manage.…”