期刊
SEMINARS IN THROMBOSIS AND HEMOSTASIS
卷 37, 期 6, 页码 698-706出版社
THIEME MEDICAL PUBL INC
DOI: 10.1055/s-0031-1291380
关键词
Inherited platelet disorder; bleeding syndrome; macrothrombocytopenia; Glanzmann thrombasthenia; integrin alpha IIb beta 3
资金
- Genoscope d'Evry [AP07/08.42]
- INSERM [ANR-08-GENO-028-03]
Glanzmann thrombasthenia (GT) is the most widely studied inherited disorder of platelets; it is caused by the absence of platelet aggregation due to quantitative and/or qualitative deficiencies of the alpha IIb beta 3 integrin coded by the ITGA2B and ITGB3 genes located at 17q21-23. Although platelet count and platelet volume (and morphology) are normal in classic GT, some reports have inferred a role for alpha IIb beta 3 in megakaryocytopoiesis and some novel but rare point mutations in either of the ITGA2B and ITGB3 genes have been associated with an altered platelet production and selective deficiencies in platelet function. This was brought to light by the discovery of mutations at Arg995 in alpha IIb and Asp723 in beta 3 that lead to platelet anisotropy (increased size variation) and thrombocytopenia. Significantly, Arg995 and Asp723 form a salt linkage binding the cytoplasmic tails of alpha IIb beta 3 together keeping the integrin in a bent resting state. Mutations weakening this link (if not abolishing it) increase the activation state of alpha IIb beta 3 and interfere with megakaryocytopoiesis. Other mutations affecting platelet production involve extracellular but membrane proximal domains of beta 3. Our purpose is to review the mutations in the ITGA2B and ITGB3 genes that lead to anisotropy and to discuss mechanisms by which this can be brought about.
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