ArticleMolecular genetics & genomic medicine2013
Demonstration of novel gain-of-function mutations of αIIbβ3: association with macrothrombocytopenia and glanzmann thrombasthenia-like phenotype.
Article in Molecular genetics & genomic medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 59 citations in OpenAlex.
- ITGA2B/ITGB3-Related Macrothrombocytopenia Associated With Gain-of-Function Mutations in ITGA2B or ITGB3 Genes.Journal of cellular and molecular medicine · 2026Review
- Optogenetic induction of subcellular CaCommunications biology · 2025Article
- Analysis of SMN protein in umbilical cord blood and postnatal peripheral blood of neonates with SMA: a rationale for prompt treatment initiation to prevent SMA development.Orphanet journal of rare diseases · 2025Article
- A nonactivatingBlood vessels, thrombosis & hemostasis · 2025Article
- PACSIN2 regulates platelet integrin β1 hemostatic function.Journal of thrombosis and haemostasis : JTH · 2023Article
- The relative importance of platelet integrins in hemostasis, thrombosis and beyond.Haematologica · 2023Review
- Diagnosing Czech Patients with Inherited Platelet Disorders.International journal of molecular sciences · 2022Article
- Rasa3 deficiency minimally affects thrombopoiesis but promotes severe thrombocytopenia due to integrin-dependent platelet clearance.JCI insight · 2022Article
- Integrins and their role in megakaryocyte development and function.Experimental hematology · 2022Review
- Specifications of the variant curation guidelines for ITGA2B/ITGB3: ClinGen Platelet Disorder Variant Curation Panel.Blood advances · 2021Article
- Glanzmann Thrombasthenia: Perspectives from Clinical Practice on Accurate Diagnosis and Optimal Treatment Strategies.Journal of blood medicine · 2021Review
- Glanzmann thrombasthenia: genetic basis and clinical correlates.Haematologica · 2020Review
- αIIbβ3 variants in ten families with autosomal dominant macrothrombocytopenia: Expanding the mutational and clinical spectrum.PloS one · 2020Article
- Genome-wide linkage analysis and whole-exome sequencing identifies an ITGA2B mutation in a family with thrombocytopenia.British journal of haematology · 2019Article
- Modulating Integrin αIIbβ3 Activity through Mutagenesis of Allosterically Regulated Intersubunit Contacts.Biochemistry · 2019Article
- [Special type of Glanzmann's thrombasthenia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2018Article
- A novel variant Glanzmann thrombasthenia due to co-inheritance of a loss- and a gain-of-function mutation ofHaematologica · 2018Article
- An intracytoplasmic β3 Leu718 deletion in a patient with a novel platelet phenotype.Blood advances · 2017Article
- A Novel Pentapeptide Targeting Integrin β3-Subunit Inhibits Platelet Aggregation and Its Application in Rat for Thrombosis Prevention.Frontiers in pharmacology · 2016Article
- Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia.Haematologica · 2016Article
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Authors and funding
8 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integrin αIIbβ3 is indispensable for normal hemostasis, but its role for thrombopoiesis is still controversial. Recently, αIIb and β3 mutations have been identified in patients with congenital macrothrombocytopenia. We analyzed three unrelated Japanese families with congenital macrothrombocytopenia. Expression and activation state of αIIbβ3 in platelets was examined by flow cytometry and immunoblotting. Sequence of whole coding region and exon-intron boundaries of ITGA2B and ITGB3 genes was performed. The effects of mutations on αIIbβ3 activation state and phosphorylation of FAK were analyzed in transfected cells. We newly identified three mutations: two mutations in highly conserved Gly-Phe-Phe-Lys-Arg sequence in juxtamembrane region of αIIb, p.Gly991Cys and p.Phe993del, and one donor site mutation of intron 13 of ITGB3 leading to 40 amino acids deletion, p.(Asp621_Glu660del), in the membrane proximal β-tail domain of β3. One patient, who showed Glanzmann thrombasthenia-like marked reduction in surface αIIbβ3 expression (3-11% of normal control), was a compound heterozygote with ITGA2B p.Gly991Cys and a novel nonsense mutation, ITGA2B p.Arg422*. All three mutations, ITGA2B p.Gly991Cys, ITGA2B p.Phe993del, and ITGB3 p.(Asp621_Glu660del), led to highly activated conformation of αIIbβ3 and spontaneous tyrosine phosphorylation of FAK in transfected cells. These results suggest that gain-of-function mutations around membrane region of αIIbβ3 lead to abnormal platelet number and morphology with impaired surface αIIbβ3 expression.
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