Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models
Top Cited Papers
- 1 December 2011
- journal article
- review article
- Published by American Society of Hematology in Blood
- Vol. 118 (23), 5996-6005
- https://doi.org/10.1182/blood-2011-07-365635
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.Keywords
This publication has 93 references indexed in Scilit:
- Kindlin-3–mediated signaling from multiple integrin classes is required for osteoclast-mediated bone resorptionThe Journal of cell biology, 2011
- Absence of preference for social novelty and increased grooming in integrin β3 knockout mice: Initial studies and future directionsAutism Research, 2011
- The Integrin Co-activator Kindlin-3 Is Expressed and Functional in a Non-hematopoietic Cell, the Endothelial CellOnline Journal of Public Health Informatics, 2010
- Structure of an integrin αIIbβ3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activationProceedings of the National Academy of Sciences of the United States of America, 2009
- The Novel S527F Mutation in the Integrin β3 Chain Induces a High Affinity αIIbβ3 Receptor by Hindering Adoption of the Bent ConformationOnline Journal of Public Health Informatics, 2009
- Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activationNature Medicine, 2009
- Structural basis for distinctive recognition of fibrinogen γC peptide by the platelet integrin αIIbβ3The Journal of cell biology, 2008
- Integrins: Bidirectional, Allosteric Signaling MachinesCell, 2002
- Enhanced pathological angiogenesis in mice lacking β3 integrin or β3 and β5 integrinsNature Medicine, 2002
- Electrostatics of nanosystems: Application to microtubules and the ribosomeProceedings of the National Academy of Sciences of the United States of America, 2001