Are bone defects in rare patients with Glanzmann's thrombasthenia associated with ITGB3 or ITGA2B mutations?

作者：Nurden Alan T^*; Fiore Mathieu; Nurden Paquita; Heilig Roland; Pillois Xavier

来源：Platelets, 2011, 22(7): 547-551.

DOI：10.3109/09537104.2011.573600

• Glanzmann thrombasthenia
• bone defects
• integrin alphavbeta3

The question as to whether Glanzmann thrombasthenia patients with ITGB3 defects and deficiencies of both alpha IIb beta 3 and alpha v beta 3 show phenotypic differences to those with abnormalities exclusive to alpha IIb beta 3 is unresolved. Studies on beta 3-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 alpha IIb, with one mutation inherited from each parent. Modelling strongly suggested that both mutations act by destabilizing the alpha IIb beta propeller. So it appears likely that this patient has a combination of co-expressed genetic defects.

• 出版日期2011