title: Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models.
abstract: Characterized by mucocutaneous bleeding arising from a lack of platelet aggregation to physiologic stimuli, Glanzmann thrombasthenia (GT) is the archetype-inherited disorder of platelets. Transmitted by autosomal recessive inheritance, platelets in GT have quantitative or qualitative deficiencies of the fibrinogen receptor, αIIbβ3, an integrin coded by the ITGA2B and ITGB3 genes. Despite advances in our understanding of the disease, extensive phenotypic variability with respect to severity and intensity of bleeding remains poorly understood. Importantly, genetic defects of ITGB3 also potentially affect other tissues, for β3 has a wide tissue distribution when present as αvβ3 (the vitronectin receptor). We now look at the repertoire of ITGA2B and ITGB3 gene defects, reexamine the relationship between phenotype and genotype, and review integrin structure in the many variant forms. Evidence for modifications in platelet production is assessed, as is the multifactorial etiology of the clinical expression of the disease. Reports of cardiovascular disease and deep vein thrombosis, cancer, brain disease, bone disorders, and pregnancy defects in GT are discussed in the context of the results obtained for mouse models where nonhemostatic defects of β3-deficiency or nonfunction are being increasingly described.
authors.affiliation: Centre de Référence des Pathologies Plaquettaires, Plateforme Technologique et d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France. alan.nurden@cnrshl.u-bordeaux2
authors.forename: Alan T
authors.initials: AT
authors.lastname: Nurden
authors.forename: Mathieu
authors.initials: M
authors.lastname: Fiore
authors.forename: Paquita
authors.initials: P
authors.lastname: Nurden
authors.forename: Xavier
authors.initials: X
authors.lastname: Pillois
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D039661:Integrin beta3 / Q000235:genetics*; D051379:Mice; D010641:Phenotype; D013915:Thrombasthenia / Q000235:genetics* / Q000473:pathology*
chemical_list: C056564:ITGA2B protein, human; C061248:ITGB3 protein, human; D039421:Integrin alpha2; D039661:Integrin beta3