title: Are bone defects in rare patients with Glanzmann's thrombasthenia associated with ITGB3 or ITGA2B mutations?
abstract: The question as to whether Glanzmann thrombasthenia patients with ITGB3 defects and deficiencies of both αIIbβ3 and αvβ3 show phenotypic differences to those with abnormalities exclusive to αIIbβ3 is unresolved. Studies on β3-deficient mice have shown an increased bone mass. Here we review the literature on bone defects in thrombasthenia patients and report the molecular analysis of a patient associating a lifelong thrombasthenia-like syndrome with skeletal defects. We show that the patient is compound heterozygote for Arg327His and Gly391Arg mutations in αIIb, with one mutation inherited from each parent. Modelling strongly suggested that both mutations act by destabilizing the αIIb beta propeller. So it appears likely that this patient has a combination of co-expressed genetic defects.
authors.affiliation: Centre de Référence des Pathologies Plaquettaires, Plateforme Technologique et d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France. alan.nurden@cnrshl.u-bordeaux2.fr
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: Roland
authors.initials: R
authors.lastname: Heilig
authors.forename: Xavier
authors.initials: X
authors.lastname: Pillois
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000150:complications / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D039421:Integrin alpha2 / Q000737:chemistry / Q000235:genetics*; D039661:Integrin beta3 / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D055550:Protein Stability; D013915:Thrombasthenia / Q000150:complications* / Q000235:genetics*
chemical_list: C056564:ITGA2B protein, human; C061248:ITGB3 protein, human; D039421:Integrin alpha2; D039661:Integrin beta3