β-1 tubulin R307H SNP alters microtubule dynamics and affects severity of a hereditary thrombocytopenia

P. A. Basciano, J. Matakas, A. Pecci, E. Civaschi, C. Cagioni, N. Bompiani, P. Burger, P. Christos, J. P. Snyder, J. Bussel, C. L. Balduini, P. Giannakakou, P. Noris

Research output: Contribution to journalArticle

Abstract

Background: Single nucleotide polymorphisms (SNPs) in platelet-associated genes partly explain inherent variability in platelet counts. Patients with monoallelic Bernard Soulier syndrome due to the Bolzano mutation (GPIBA A156V) have variable platelet counts despite a common mutation for unknown reasons. Objectives: We investigated the effect of the most common SNP (R307H) in the hematopoietic-specific tubulin isotype β-1 in these Bernard Soulier patients and potential microtubule-based mechanisms of worsened thrombocytopenia. Patients/Methods: Ninety-four monoallelic Bolzano mutation patients were evaluated for the R307H β-1 SNP and had platelet counts measured by three methods; the Q43P SNP was also evaluated. To investigate possible mechanisms underlying this association, we used molecular modeling of β-1 tubulin with and without the R307H SNP. We transfected SNP or non-SNP β-1 tubulin into MCF-7 and CMK cell lines and measured microtubule regrowth after nocodazole-induced depolymerization. Results: We found that patients with at least one R307H SNP allele had significantly worse thrombocytopenia; manual platelet counting revealed a median platelet count of 124 in non-SNP patients and 76 in SNP patients (both ×109 L-1; P 

Original languageEnglish
Pages (from-to)651-659
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume13
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

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Keywords

  • Bernard-Soulier syndrome
  • Beta-tubulin
  • Cytoskeleton
  • Microtubules
  • Polymorphism, single nucleotide

ASJC Scopus subject areas

  • Hematology

Cite this

Basciano, P. A., Matakas, J., Pecci, A., Civaschi, E., Cagioni, C., Bompiani, N., Burger, P., Christos, P., Snyder, J. P., Bussel, J., Balduini, C. L., Giannakakou, P., & Noris, P. (2015). β-1 tubulin R307H SNP alters microtubule dynamics and affects severity of a hereditary thrombocytopenia. Journal of Thrombosis and Haemostasis, 13(4), 651-659. https://doi.org/10.1111/jth.12824