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

作者：Vettore Silvia; Tezza Fabiana; Malara Alessandro; Vianello Fabrizio; Pecci Alessandro; Scandellari Raffaella; Floris Matteo; Balduini Alessandra; Fabris Fabrizio^*

来源：Haematologica-The Hematology Journal, 2011, 96(12): 1878-1882.

DOI：10.3324/haematol.2010.039008

• Bernard-Soulier
• congenital thrombocytopenia
• glycoprotein Ib alpha
• platelets

Platelet glycoprotein GPIb alpha mutations are the basic defect behind Bernard-Soulier syndrome, a rare inherited macrothrombocytopenia characterized by anomalies of the GPIb alpha, GPIb beta 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 GPIb alpha, 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 GPIb alpha mRNA was not detectable. GPIX protein was slightly reduced and GPIb beta 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 GPIb alpha transcript. The c.386A>G mutation suggests a unique mutational mechanism causing the virtual absence of GPIb alpha without creating a stop codon.

• 出版日期2011-12