title: Understanding the genetic basis of Glanzmann thrombasthenia: implications for treatment.
abstract: Glanzmann thrombasthenia (GT) is characterized by mucocutaneous bleeding due to platelets that fail to aggregate in response to physiologic stimuli. GT, a rare inherited disease, is caused by quantitative or qualitative deficiencies of αIIbβ3, an integrin receptor for adhesive proteins. Coded by the ITGA2B and ITGB3 genes, αIIbβ3 mediates platelet-to-platelet attachment, aggregation and clot retraction. Despite widespread mutation analysis, the reason for the extensive variation in both the severity and intensity of bleeding among affected individuals remains poorly understood. Although genetic defects of ITGB3 affect other tissues where β3 is present as αvβ3 (the vitronectin receptor), the bleeding phenotype continues to dominate. The authors now examine the relationship between genotype and phenotype in classic and variant forms of GT, and reassess if the nature of the gene mutation influences bleeding and treatment aimed at restoring hemostasis.
authors.affiliation: Plateforme Technologique et d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France. nurdenat@gmail.com
authors.forename: Alan T
authors.initials: AT
authors.lastname: Nurden
authors.forename: Xavier
authors.initials: X
authors.lastname: Pillois
authors.forename: Paquita
authors.initials: P
authors.lastname: Nurden
mesh_terms: D006801:Humans; D039421:Integrin alpha2 / Q000737:chemistry / Q000235:genetics*; D039302:Integrin alphaVbeta3 / Q000737:chemistry / Q000235:genetics; D039661:Integrin beta3 / Q000737:chemistry / Q000235:genetics*; D009154:Mutation; D010974:Platelet Aggregation; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D013915:Thrombasthenia / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy
chemical_list: C056564:ITGA2B protein, human; C061248:ITGB3 protein, human; D039421:Integrin alpha2; D039302:Integrin alphaVbeta3; D039661:Integrin beta3