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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Basani, R. B. Articles by Poncz, M. Search for Related Content PubMed PubMed Citation Articles by Basani, R. B. Articles by Poncz, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  A Leu117  Trp Mutation Within the RGD-Peptide Cross-Linking Region of 3 Results in Glanzmann Thrombasthenia by Preventing IIb3 Export to the Platelet Surface Ramesh B. Basani, Deborah L. Brown, Gaston Vilaire, Joel S. Bennett, and Mortimer Poncz From the Departments of Pediatrics and Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA. We report a case of Glanzmann thrombasthenia in a Pakistani child whose platelets express less than 10% of the normal amount of IIb3 on their surface. Single-stranded conformation polymorphism analysis of the exons of the patient's IIb and 3 genes showed an abnormality in exon 4 of the 3 gene. Direct sequence analysis showed that the patient was homozygous for a T  G nucleotide substitution in this exon, resulting in the replacement of a highly conserved Leu at position 117 with Trp. Heterologous expression of IIb3 containing the 3 mutation in COS-1 cells confirmed the pathogenicity of the Leu117  Trp substitution and showed that it resulted in the intracellular retention of malfolded IIb3 heterodimers. Additional site-directed mutagenesis at position 117 indicated that, although the smaller hydrophobic amino acid Val could be substituted for the wild-type Leu, the larger hydrophobic amino acids Trp and Phe or the charged amino acids Asp and Lys were not tolerated. These studies indicate that Leu117 in 3 plays a critical role in attaining the correct folded conformation of IIb3. These studies also suggest that the hydrophobic side chain of Leu117 is likely folded into the interior of 3, where it serves to stabilize internal packing of the protein and determines its overall shape. Blood, Vol. 90 No. 8 (July 15), 1997: pp. 3082-3088 © 1997 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Jallu, M. Meunier, M. Brement, and C. Kaplan A new platelet polymorphism Duva+, localized within the RGD binding domain of glycoprotein IIIa, is associated with neonatal thrombocytopenia Blood, May 29, 2002; 99(12): 4449 - 4456. [Abstract] [Full Text] [PDF] A. Cierniewska-Cieslak, C. S. Cierniewski, K. Blecka, M. Papierak, L. Michalec, L. Zhang, T. A. Haas, and E. F. Plow Identification and Characterization of Two Cation Binding Sites in the Integrin beta 3 Subunit J. Biol. Chem., March 22, 2002; 277(13): 11126 - 11134. [Abstract] [Full Text] [PDF] S. Tadokoro, Y. Tomiyama, S. Honda, H. Kashiwagi, S. Kosugi, M. Shiraga, T. Kiyoi, Y. Kurata, and Y. Matsuzawa Missense mutations in the beta 3 subunit have a different impact on the expression and function between alpha IIbbeta 3 and alpha vbeta 3 Blood, February 1, 2002; 99(3): 931 - 938. [Abstract] [Full Text] [PDF] M. K. Boudreaux and D. L. Lipscomb Clinical, Biochemical, and Molecular Aspects of Glanzmann's Thrombasthenia in Humans and Dogs Vet. Pathol., May 1, 2001; 38(3): 249 - 260. [Abstract] [Full Text] [PDF] D Inwald, E G Davies, and N Klein Demystified ...: Adhesion molecule deficiencies Mol. Pathol., February 1, 2001; 54(1): 1 - 7. [Abstract] [Full Text] D. T.-L. Roux, V. Roullot, C. Poujol, T. Kortulewski, P. Nurden, and G. Marguerie Thrombasthenic mice generated by replacement of the integrin alpha IIb gene: demonstration that transcriptional activation of this megakaryocytic locus precedes lineage commitment Blood, August 15, 2000; 96(4): 1399 - 1408. [Abstract] [Full Text] [PDF] D. L. French and U. Seligsohn Platelet Glycoprotein IIb/IIIa Receptors and Glanzmann’s Thrombasthenia Arterioscler. Thromb. Vasc. Biol., March 1, 2000; 20(3): 607 - 610. [Full Text] [PDF] S. Tadokoro, Y. Tomiyama, S. Honda, M. Arai, N. Yamamoto, M. Shiraga, S. Kosugi, Y. Kanakura, Y. Kurata, and Y. Matsuzawa A Gln747right-arrowPro Substitution in the alpha IIb Subunit Is Responsible for a Moderate alpha IIbbeta 3 Deficiency in Glanzmann Thrombasthenia Blood, October 15, 1998; 92(8): 2750 - 2758. [Abstract] [Full Text] [PDF] E. F. Plow, T. A. Haas, L. Zhang, J. Loftus, and J. W. Smith Ligand Binding to Integrins J. Biol. Chem., July 14, 2000; 275(29): 21785 - 21788. [Full Text] [PDF]

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