Thrombasthenia mutations

Fig.2. Glanzmaim thrombasthenia mutations within the GPma sequence including the MIDAS-like motif. The amino terminal sequence of GPIIIa from residues 110-289 showing the residues (in bold) that form the MIDAS-like motif . The Glanzmann thomba enia mutations are shown under the sequence and are listed by the patient designations as represented in Table 2.

Fig. 3 Glanzmann thrombasthenia mutations within the P-propeller stiucture of GPIIb A schematic drawing of the GPIIb p-propeller structural model showing the P-strands (arrows) and connecting strand arrangements . The propeller is drawn like a cylinder and each blade of the propeller is labeled W1-W7. The P-strands are numbered 1-4 with the first strand located toward the center and bottom and the fourth strand located outside and top of the cylinder. Hie wide ribbons represent the connections between the fourth P-strand of one blade and the first p-strand of the next blade. The ladder-like connections represent the calcium-binding domains and are located on the bottom of the cylinder. The Glanzmann thrombasthenia mutations are represented by black dots and the black bar in W2 represents an intradisulfide bond.

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Chen Y-P, Djaffar I, Pidard D, Steiner B, Cieutat A-M, Caen JP, Rosa J-P Ser-7522Pro mutation in the cytoplasmic domain of int rin b, subunit and defective activation of platelet integrin a ,b, (glycoprotein lib-IIIa) in a variant of Glanzmann thrombasthenia. ProcNatl Acad Sd USA 89 10169-10173,1 2. 

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Grimaldi CM, Chen FP, Scudder LE, Coller BS, French DL A Cys374Tyr homozygous mutation of platelet glycoprotein ina(b,) in a Chinese patient with Glanzmann s thrombasthenia Blood 88 1666-1675, 1996. 

French DL, Chen F, Xu L, Coller BS A common Arg584Stop mutation in glycoprotein (GP) lib in 2 additional patients with Glanzmatm thrombasthenia Blood 88 30a, 1996 (Abstract). 

French DL, Chen FP, Xu L, Weiss HJ, CoUer BS Two uiuelated doubly hetero gous patients with Glanzmann thrombasthenia have the same GPIIb mutation resulting in loss of the transmembrane domain. Thromb Haemost 77 360,1997 (Abstract). 

Grimaldi CM, Chen FP, Wu CH, Weiss HJ, CoUer BS, French DL Glycoprotein lib Leu214Pro mutation prcxluces Glanzmaim thrombasthenia with both c]uantitative and qualitative abnormalities in GPlIb/IlIa Blood 91 1562-1571,1998. 

Basani R, Bennett i,PonczM A Glanzmann thrombasthenia variant due to an a, mutation suggests that an additional N-terminal loop is involved in ligand-binding. Blood 90 26a, 1997 (Abstract). 

Gu JM, Xu WF, Wang XD, Wu QY, Chi CW, Ruan CG Identification of a nonsense mutation at amino add 584-arginine of platelet glycoprotein Hb in patients with type I Glanzmann thrombasthenia. J Haematol 83 442-449,1993. 

Tomiyama Y, Kashiwagi H, Kosugi S, Shiraga M, Kanayama Y, Kurata Y, Matsuzawa Y Atmormal processing of the glycoprotein lib transcript due to a nonsense mutation in exon 17 assodated with Glanzmann s thrombasthenia Thromb Haemost 73 756-762,1995. 

Iwamoto S, Nishiumi E, Kajii E, Ikonoto S An exon 28 mutation resulting in alternative splicing of the glycoprotein Ilb transcript and Glanzmann s thrombasthenia Blood 83 1017-1023,1994. 

Basani RB, Brown DL, Vilaire G, Bennett JS, Poncz M A Leu" y Trp mutation within the RGD-peptide cross-linking region of b, results in Glanzmann thrombasthenia by preventing a Jb, export to theplatdet surface. Blood 90 3082-3088,1997. 

Peyruchaud O, Nurden AT, Bourre F Use of PCR-SSCP to screen the exons of the GP lib and GP Ilia genes of a variant with Glanzmann thrombasthenia A mutation in the nucleotide sequence for die GFFKR cytoplasmic domain of the integrin subunit a, (GPIIb). Thromb Haonost 73 1189,1995 (Abstract). 

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