Glycoprotein lb Polymorphism in a Patient with Glanzmann’s Thrombasthenia Type I (Case Report)

SummaryWe analyzed the molecular genetic defect responsible for type I Glanzmann’s thrombasthenia in a Japanese patient. In an immunoblot assay using polyclonal anti-GPIIb-IIIa antibodies, some GPIIIa (15% of normal amount) could be detected in the patient’s platelets, whereas GPIIb could not (<2% of normal amount). Nucleotide sequence analysis of platelet GPIIb mRNA-derived polymerase chain reaction (PCR) products revealed that patient’s GPIIb cDNA had a 75-bp deletion in the 3’ boundary of exon 17 resulting in an in-frame deletion of 25 amino acids. DNA analysis and family study revealed that the patient was a compound heterozygote of two GPIIb gene defects. One allele derived from her father was not expressed in platelets, and the other allele derived from her mother had a 9644C → T mutation which was located at the position -3 of the splice donor junction of exon 17 and resulted in a termination codon (TGA). Moreover, quantitative analysis demonstrated that the amount of the abnormal GPIIb transcript in the patient’s platelets was markedly reduced. Thus, the C → T mutation resulting in the abnormal splicing of GPIIb transcript and the reduction in its amount is responsible for Glanzmann’s thrombasthenia.

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Detection of Carriers in Glanzmann's Thrombasthenia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657357 ◽

1983 ◽

Vol 49 (03) ◽

pp. 182-186

Author(s):

G T E Zonneveld ◽

E F van Leeuwen ◽

A Sturk ◽

J W ten Cate

Keyword(s):

Bleeding Time ◽

Periodic Acid ◽

Type I ◽

Clot Retraction ◽

Periodic Acid Schiff ◽

Glanzmann’S Thrombasthenia ◽

Aggregation Response ◽

Glanzmann's Thrombasthenia ◽

Sds Page ◽

Reduced State

SummaryQuantitative glycoprotein (GP) analysis of whole platelets or platelet membranes was performed by SDS-polyacrylamide gelelectrophoresis (SDS-PAGE) and periodic acid Schiff staining in the families of two unrelated Glanzmann’s thrombasthenia (GT) patients. Each family consisted of two symptom free parents, a symptom free daughter and a GT daughter. All symptom free members had a normal bleeding time, clot retraction and platelet aggregation response to adenosine 5’-diphosphate (ADP), collagen and adrenalin. Platelet Zw* antigen was normally expressed in these subjects. GT patiens, classified as a type I and II subject, showed reduced amounts of GP lib and of GP nia. Analysis of isolated membranes in the non-reduced state, however, showed that the amount of GP Ilia was also reduced in three of the four parents, whereas one parent (of the GT type I patient) and the two unaffected daughters had normal amounts of GP Ilia. Quantitative SDS-PAGE may therefore provide a method for the detection of asymptomatic carriers in GT type I and II.

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A Case Report on Glanzmann’s Thrombasthenia: A Rare Platelet Function Disorder

Haematology Journal of Bangladesh ◽

10.37545/haematoljbd201818 ◽

2018 ◽

Vol 2 (02) ◽

pp. 59-60

Author(s):

Farida Yasmin ◽

Md. Anwarul Karim ◽

Chowdhury Yakub Jamal ◽

Mamtaz Begum ◽

Ferdousi Begum

Keyword(s):

Case Report ◽

Platelet Function ◽

The Body ◽

Presenting Symptoms ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia ◽

Platelet Function Disorders ◽

Recurrent Epistaxis ◽

Severe Epistaxis ◽

History Of

Epistaxis in children is one of the important presenting symptoms for attending emergency department in paediatric patients. Recurrent epistaxis is common in children. Although epistaxis in children usually occurred due to different benign conditions, it may be one of the important presenting symptoms of some inherited bleeding disorder. Whereas most bleeding disorders can be diagnosed through different standard hematologic assessments, diagnosing rare platelet function disorders may be challenging. In this article we describe one case report of platelet function disorders on Glanzmann’s thrombasthenia (GT). Our patient was a 10-year old girl who presented to us with history of recurrent severe epistaxis. She had a bruise on her abdomen and many scattered petechiae in different parts of the body. Her previous investigations revealed no demonstrable haemostatic anomalies. After performing platelet aggregation test, she was diagnosed as GT.

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Two Genetic Defects in αIIbAre Associated with Type I Glanzmann's Thrombasthenia in a Great Pyrenees Dog: A 14-base Insertion in Exon 13 and a Splicing Defect of Intron 13

Veterinary Pathology ◽

10.1354/vp.37-6-581 ◽

2000 ◽

Vol 37 (6) ◽

pp. 581-588 ◽

Cited By ~ 26

Author(s):

D. L. Lipscomb ◽

C. Bourne ◽

M. K. Boudreaux

Keyword(s):

Genetic Defects ◽

Type I ◽

Glanzmann’S Thrombasthenia ◽

Splicing Defect ◽

Glanzmann's Thrombasthenia ◽

Base Insertion

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Anesthetic Management of a Patient with Glanzmann's Thrombasthenia - A case report -

Korean Journal of Anesthesiology ◽

10.4097/kjae.2007.53.3.407 ◽

2007 ◽

Vol 53 (3) ◽

pp. 407

Author(s):

Min-Woo Jeong ◽

Kwang-Suk Seo ◽

Hyun-Jeong Kim ◽

Kwang-Won Yum

Keyword(s):

Case Report ◽

Anesthetic Management ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia

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Homozygous Cys542Arg substitution in GPIIIa in a Swiss patient with type I Glanzmann's thrombasthenia

British Journal of Haematology ◽

10.1111/j.1365-2141.1999.01376.x ◽

1999 ◽

Vol 105 (2) ◽

pp. 523-531 ◽

Cited By ~ 15

Author(s):

Jian Ruan ◽

Markus Schmugge ◽

Kenneth J. Clemetson ◽

Eric Cazes ◽

Robert Combrie ◽

...

Keyword(s):

Type I ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia

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A Three Amino Acid Deletion in Glycoprotein IIIa Is Responsible for Type I Glanzmann's Thrombasthenia: Importance of Residues Ile325Pro326Gly327 for β3 Integrin Subunit Association

Blood ◽

10.1182/blood.v90.2.669 ◽

1997 ◽

Vol 90 (2) ◽

pp. 669-677 ◽

Cited By ~ 17

Author(s):

Marie-Christine Morel-Kopp ◽

Cécile Kaplan ◽

Valérie Proulle ◽

Vincent Jallu ◽

Chantal Melchior ◽

...

Keyword(s):

Amino Acid ◽

Restriction Site ◽

Restriction Analysis ◽

Enzyme Linked Immunosorbent Assay ◽

Type I ◽

Integrin Subunit ◽

Wild Type ◽

Amino Acid Deletion ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia

Abstract Glanzmann's thrombasthenia (GT) is a recessive autosomal bleeding disorder characterized by abnormal platelet aggregation due to a qualitative or quantitative defect of the glycoprotein (GP) IIb-IIIa complex (integrin αIIbβ3). We describe a new mutation in the GPIIIa gene responsible for type I GT in a consanguineous Algerian family. A discordance between phenotyping and genotyping of the GPIIIa-related HPA-1 platelet alloantigen system in three family members heterozygous for the disease suggested a genetic defect in the GPIIIa gene and a normal GPIIb gene. Sequence analysis of amplified genomic DNA fragments showed a 6-bp deletion in exon 7 of the GPIIIa gene resulting in the amino acid deletion/substitution (Ile325Pro326Gly327 → Met) and creating a new BspHI restriction site. Expression of the mutated integrin β3 subunit cDNA in Chinese hamster ovary cells showed that the cDNA gene was transcribed into a full-length β3 protein with an apparent molecular weight identical to wild-type β3 and accumulated as a single-chain molecule in the cell cytoplasm. The absence of heterodimeric complex formation of the mutant β3 protein with endogeneous αv was shown by immunoprecipitation experiments, intracellular immunofluorescent labeling, and a semiquantitative enzyme-linked immunosorbent assay using the αvβ3 complex-specific monoclonal antibodies LM609 and 23C6. Substitution of the methionine residue by a proline, present at position 326 of wild-type β3, did not restore the ability of the recombinant mutant β3 protein to associate with αv, suggesting that the Ile-Pro-Gly motif is located in a β3 domain important for integrin subunit interaction. The association of a BspHI restriction site with this newly identified mutation has allowed allele-specific restriction analysis of Algerian GT individuals and the identification of two new unrelated type I patients exhibiting the same mutation, suggesting that the described mutation might be significant in this population and that BspHI restriction analysis will provide a useful screening assay for antenatal diagnosis and genetic counselling.

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Indication for allogeneic stem cell transplantation in Glanzmann’s thrombasthenia

Hämostaseologie ◽

10.5482/hamo-12-08-0014 ◽

2013 ◽

Vol 33 (04) ◽

pp. 305-312 ◽

Cited By ~ 12

Author(s):

K. Sauer ◽

B. Winkler ◽

M. Eyrich ◽

P. G. Schlegel ◽

V. Wiegering

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autosomal Recessive Disorder ◽

Marrow Transplant ◽

Haematopoietic Stem Cell ◽

Current Status ◽

Type I ◽

Glanzmann’S Thrombasthenia ◽

Glanzmann's Thrombasthenia

SummaryGlanzmann’s thrombasthenia (GT) is an autosomal recessive disorder characterized by a lack of thrombocyte aggregation due to the absence of thrombocyte glycoproteins IIb and αIIbβ3. The role of haematopoietic stem cell transplantation (HSCT) in GT remains controversial. However, HSCT offers the only curative approach for patients with a severe clinical phenotype.In this review, we will discuss the limitation of current status evidence and the specific risk of GT, in particular the alloimmunization and refractoriness to thrombocyte infusions. 19 successful HSCT in 18 GT type I patients have been reported. Mean age at transplantation was 5 years. All patients are still alive. The majority received sibling bone marrow transplant with busulfan and cyclophosphamid conditioning. GvHD incidence was within the normal range, but 10 patients showed alloimmunization of thrombocytes. Median follow up is 25 months.

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