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A A386G biallelic GPIbα gene mutation with anomalous behavior: a new mechanism suggested for Bernard-Soulier syndrome pathogenesis

Silvia Vettore, Fabiana Tezza, Alessandro Malara, Fabrizio Vianello, Alessandro Pecci, Raffaella Scandellari, Matteo Floris, Alessandra Balduini, Fabrizio Fabris
Haematologica - 2011
Platelet glycoprotein GPIbα mutations are the basic defect behind Bernard-Soulier syndrome, a rare inherited macrothrombocytopenia characterized by anomalies of the GPIbα, GPIbβ and GPIX subunits of von Willebrand factor receptor. A 32-year old man was investigated for suspected Bernard-Soulier syndrome. Ristocetin induced agglutination was absent. Flow cytometry and Western blot analysis showed a severe reduction in GPIbα, but sequencing revealed only a biallelic c.386A>G substitution, theoretically leading to a p.Asn110Glu variation. To further clarify the data, megakaryocyte cultures were set. Though the maturation of megakaryocytes was normal, proplatelet formation was defective and GPIbα mRNA was not detectable. GPIX protein was slightly reduced and GPIbβ polypeptide almost absent. Computational analysis showed that the c.386A>G mutation disrupted an exon splicing enhancer motif involved in the proper maturation of the GPIbα transcript. The c.386A>G mutation suggests a unique mutational mechanism causing the virtual absence of GPIbα without creating a stop codon.

BibTex references

@Article{VTMVPSFBF11,
  author       = {Vettore, S. and Tezza, F. and Malara, A. and Vianello, F. and Pecci, A. and Scandellari, R. and Floris, M. and Balduini, A. and Fabris, F.},
  title        = {A A386G biallelic GPIbα gene mutation with anomalous behavior: a new mechanism suggested for Bernard-Soulier syndrome pathogenesis},
  journal      = {Haematologica},
  year         = {2011},
  publisher    = {Ferrata Storti Foundation},
  keywords     = {Alternative splicing, mutation},
  doi          = {10.3324/haematol.2010.039008},
  url          = {http://publications.crs4.it/pubdocs/2011/VTMVPSFBF11},
}

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» Silvia Vettore
» Matteo Floris