Bernard-Soulier Syndrome due to Compound Heterozygosity for a Novel Glycoprotein Ib� Mutation

2014 ◽  
Vol 131 (1) ◽  
pp. 46-49 ◽  
Author(s):  
Tetsuji Sato ◽  
Shinji Kunishima ◽  
Rie Shirayama ◽  
Shun Ichikawa ◽  
Michio Sakai ◽  
...  
Keyword(s):  
Compound Heterozygosity ◽  
Glycoprotein Ib ◽  
Bernard Soulier Syndrome

scholarly journals Residual amounts of glycoprotein Ib concomitant with near-absence of glycoprotein IX in platelets of Bernard-Soulier patients

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 1086-1088 ◽  
Author(s):  
J Drouin ◽  
JL McGregor ◽  
S Parmentier ◽  
CA Izaguirre ◽  
KJ Clemetson
Keyword(s):  
Normal Level ◽  
Polyclonal Antibodies ◽  
Band Pattern ◽  
Platelet Membrane ◽  
Membrane Glycoprotein ◽  
Glycoprotein Ib ◽  
Gene Deletions ◽  
Immunoblot Assay ◽  
Platelet Membrane Glycoprotein ◽  
Bernard Soulier Syndrome

A study of the Bernard-Soulier syndrome in two unrelated families using different polyclonal antibodies in a sensitive immunoblot assay showed residual amounts of platelet membrane glycoprotein (GP) lb in the eight homozygotes, as well as the near-absence of GPlb beta and GPIX. The eight heterozygotes studied showed a double band pattern for GPlb and about half the normal level of GPlb beta and GPIX. Therefore, we conclude that the Bernard-Soulier syndrome is heterogeneous and is probably not due to gene deletions.

The cysteine knot of platelet glycoprotein Ibβ (GPIbβ) is critical for the interaction of GPIbβ with GPIX

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4428-4433 ◽  
Author(s):  
Dermot Kenny ◽  
Patricia A. Morateck ◽  
Robert R. Montgomery
Keyword(s):  
Amino Acids ◽  
Monoclonal Antibody ◽  
Mammalian Cells ◽  
Surface Expression ◽  
Terminal Region ◽  
Platelet Glycoprotein ◽  
Glycoprotein Ib ◽  
N Terminus ◽  
Bernard Soulier Syndrome

The glycoprotein Ib (GPIb) complex is composed of GPIbα covalently attached to GPIbβ and noncovalently complexed with GPIX and GPV. Patients with Bernard-Soulier syndrome demonstrate that mutations in either GPIbβ or GPIX result in an absence of platelet GPIbα. This occurs through the interaction of GPIX with GPIbβ. The precise sites of interaction of GPIbβ with GPIX are not known. To characterize the interaction of GPIbβ and GPIX, we developed an anti-GPIbβ monoclonal antibody MBC 257.4, whose epitope was in the N-terminal region of GPIbβ. N-terminal truncations of GPIbβ were expressed in mammalian cells. N-terminal truncations of GPIbβ, missing the first 14, 26, or 31 amino acids, were surface-expressed but did not enable coexpressed GPIX to be surface expressed, suggesting that the site of interaction with GPIX was modified by these deletions. GPIbβ and GPIX chimeras corresponding to predicted boundaries were used to define the sites of interaction of GPIbβ with GPIX. Replacing the N-terminal disulfide loops of GPIbβ (amino acids 1-14) with the corresponding disulfide loops of GPIX (amino acids 1-22) resulted in surface expression of coexpressed wildtype GPIX. However, when the N terminus of GPIbβ was replaced to residue 32 with the N terminus of GPIX (amino acids 1-36), GPIX did not surface express with this chimera. These results suggest that the cysteine knot region of GPIbβ in the N terminus is critical for the conformation of GPIbβ that interacts with GPIX and further suggests that a critical interaction of GPIbβ with GPIX involve residues 15 through 32 of GPIbβ.

scholarly journals Pseudo-Bernard-Soulier syndrome: thrombocytopenia caused by autoantibody to platelet glycoprotein Ib

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 428-431
Author(s):  
DV Devine ◽  
MS Currie ◽  
WF Rosse ◽  
CS Greenberg
Keyword(s):  
Immunoglobulin G ◽  
Adenosine Diphosphate ◽  
Platelet Glycoprotein ◽  
Laboratory Studies ◽  
Antiplatelet Antibody ◽  
Glycoprotein Ib ◽  
Immune Mediated ◽  
Induced Aggregation ◽  
Willebrand Factor ◽  
Bernard Soulier Syndrome

The Bernard-Soulier syndrome is an inherited bleeding disorder that is due to a deficiency in platelet glycoprotein Ib. Bernard-Soulier platelets fail to agglutinate in response to ristocetin despite normal levels of factor VIII:von Willebrand factor. We report a patient who developed severe refractory thrombocytopenia postsurgically while receiving procainamide therapy. Thrombocytopenia was immune mediated since the patient's platelets bore high levels of antiplatelet antibody. Radioimmunoprecipitation studies demonstrated that the autoantibodies had specificity for platelet glycoproteins Ib and V as well as platelet HLA. The patient's plasma as well as purified immunoglobulin G completely inhibited the ristocetin-induced aggregation of normal platelets but did not inhibit adenosine diphosphate-induced aggregation. The laboratory studies revealed that this patient suffered from antibody-mediated thrombocytopenia with unusual characteristics that we have called pseudo-Bernard-Soulier syndrome.

scholarly journals Point mutation in a leucine-rich repeat of platelet glycoprotein Ib alpha resulting in the Bernard-Soulier syndrome.

1993 ◽  
Vol 92 (3) ◽  
pp. 1213-1220 ◽  
Author(s):  
J Ware ◽  
S R Russell ◽  
P Marchese ◽  
M Murata ◽  
M Mazzucato ◽  
...  
Keyword(s):  
Point Mutation ◽  
Platelet Glycoprotein ◽  
Leucine Rich Repeat ◽  
Glycoprotein Ib ◽  
Bernard Soulier Syndrome

scholarly journals Pseudo-Bernard-Soulier syndrome: thrombocytopenia caused by autoantibody to platelet glycoprotein Ib

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 428-431 ◽  
Author(s):  
DV Devine ◽  
MS Currie ◽  
WF Rosse ◽  
CS Greenberg
Keyword(s):  
Immunoglobulin G ◽  
Adenosine Diphosphate ◽  
Platelet Glycoprotein ◽  
Laboratory Studies ◽  
Antiplatelet Antibody ◽  
Glycoprotein Ib ◽  
Immune Mediated ◽  
Induced Aggregation ◽  
Willebrand Factor ◽  
Bernard Soulier Syndrome

Abstract The Bernard-Soulier syndrome is an inherited bleeding disorder that is due to a deficiency in platelet glycoprotein Ib. Bernard-Soulier platelets fail to agglutinate in response to ristocetin despite normal levels of factor VIII:von Willebrand factor. We report a patient who developed severe refractory thrombocytopenia postsurgically while receiving procainamide therapy. Thrombocytopenia was immune mediated since the patient's platelets bore high levels of antiplatelet antibody. Radioimmunoprecipitation studies demonstrated that the autoantibodies had specificity for platelet glycoproteins Ib and V as well as platelet HLA. The patient's plasma as well as purified immunoglobulin G completely inhibited the ristocetin-induced aggregation of normal platelets but did not inhibit adenosine diphosphate-induced aggregation. The laboratory studies revealed that this patient suffered from antibody-mediated thrombocytopenia with unusual characteristics that we have called pseudo-Bernard-Soulier syndrome.

scholarly journals A murine antiglycoprotein Ib complex monoclonal antibody, SZ 2, inhibits platelet aggregation induced by both ristocetin and collagen

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 570-577 ◽  
Author(s):  
CG Ruan ◽  
XP Du ◽  
XD Xi ◽  
PA Castaldi ◽  
MC Berndt
Keyword(s):  
Monoclonal Antibody ◽  
Platelet Aggregation ◽  
Binding Sites ◽  
Human Platelet ◽  
Platelet Glycoprotein ◽  
Scatchard Analysis ◽  
Type I ◽  
Glycoprotein Ib ◽  
Induced Aggregation ◽  
Bernard Soulier Syndrome

Abstract A new monoclonal antibody (MoAb), SZ 2, reactive with the human platelet glycoprotein Ib complex has been produced by the hybridoma technique. SZ 2 immunoprecipitated the components of the glycoprotein Ib complex, glycoprotein Ib and glycoprotein IX, from Triton-X-100- solubilized, periodate-labeled platelets. Western blot analysis indicated that the epitope for SZ 2 was on the alpha-subunit of glycoprotein Ib. Scatchard analysis of SZ 2 binding to formaldehyde- fixed, washed platelets revealed a single class of binding sites with Kd = 6.6 +/- 3.3 X 10(-10) mol/L and 15,200 +/- 4,100 binding sites per platelet (mean +/- SD, n = 10). Intact antibody and its purified (Fab')2 fragments not only inhibited the ristocetin-dependent binding of von Willebrand factor to platelets and ristocetin-induced platelet agglutination but also inhibited platelet aggregation induced by Type I collagen and platelet-activating factor (PAF). SZ 2 inhibited platelet serotonin and beta-thromboglobulin release in response to these stimuli and also platelet thromboxane A2 formation in response to ristocetin and collagen. SZ 2 was without effect on platelet aggregation or release in response to other platelet stimuli such as ADP, thrombin, or arachidonic acid. The inhibition by SZ 2 of collagen- and PAF-induced platelet aggregation is surprising in that Bernard-Soulier syndrome platelets, which lack the glycoprotein Ib complex, respond normally to both these stimuli. SZ 2 was unreactive toward Bernard-Soulier syndrome platelets, as evaluated by fluorescence-associated cell sorting, and had no effect on the collagen- and PAF-induced aggregation of Bernard- Soulier syndrome platelets. The combined results suggest that the inhibition by SZ 2 of collagen- and PAF-induced aggregation of normal platelets is steric and are consistent with the glycoprotein Ib complex and the platelet collagen and PAF receptor(s) being adjacent in the human platelet plasma membrane.

scholarly journals A murine antiglycoprotein Ib complex monoclonal antibody, SZ 2, inhibits platelet aggregation induced by both ristocetin and collagen

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 570-577 ◽  
Author(s):  
CG Ruan ◽  
XP Du ◽  
XD Xi ◽  
PA Castaldi ◽  
MC Berndt
Keyword(s):  
Monoclonal Antibody ◽  
Platelet Aggregation ◽  
Binding Sites ◽  
Human Platelet ◽  
Platelet Glycoprotein ◽  
Scatchard Analysis ◽  
Type I ◽  
Glycoprotein Ib ◽  
Induced Aggregation ◽  
Bernard Soulier Syndrome

A new monoclonal antibody (MoAb), SZ 2, reactive with the human platelet glycoprotein Ib complex has been produced by the hybridoma technique. SZ 2 immunoprecipitated the components of the glycoprotein Ib complex, glycoprotein Ib and glycoprotein IX, from Triton-X-100- solubilized, periodate-labeled platelets. Western blot analysis indicated that the epitope for SZ 2 was on the alpha-subunit of glycoprotein Ib. Scatchard analysis of SZ 2 binding to formaldehyde- fixed, washed platelets revealed a single class of binding sites with Kd = 6.6 +/- 3.3 X 10(-10) mol/L and 15,200 +/- 4,100 binding sites per platelet (mean +/- SD, n = 10). Intact antibody and its purified (Fab')2 fragments not only inhibited the ristocetin-dependent binding of von Willebrand factor to platelets and ristocetin-induced platelet agglutination but also inhibited platelet aggregation induced by Type I collagen and platelet-activating factor (PAF). SZ 2 inhibited platelet serotonin and beta-thromboglobulin release in response to these stimuli and also platelet thromboxane A2 formation in response to ristocetin and collagen. SZ 2 was without effect on platelet aggregation or release in response to other platelet stimuli such as ADP, thrombin, or arachidonic acid. The inhibition by SZ 2 of collagen- and PAF-induced platelet aggregation is surprising in that Bernard-Soulier syndrome platelets, which lack the glycoprotein Ib complex, respond normally to both these stimuli. SZ 2 was unreactive toward Bernard-Soulier syndrome platelets, as evaluated by fluorescence-associated cell sorting, and had no effect on the collagen- and PAF-induced aggregation of Bernard- Soulier syndrome platelets. The combined results suggest that the inhibition by SZ 2 of collagen- and PAF-induced aggregation of normal platelets is steric and are consistent with the glycoprotein Ib complex and the platelet collagen and PAF receptor(s) being adjacent in the human platelet plasma membrane.

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