title: A A386G biallelic GPIbα gene mutation with anomalous behavior: a new mechanism suggested for Bernard-Soulier syndrome pathogenesis.
abstract: 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.
authors: Department of Medical and Surgical Sciences, University of Padua Medical School, Padova, Italy.
authors: Silvia
authors: S
authors: Vettore
authors: Fabiana
authors: F
authors: Tezza
authors: Alessandro
authors: A
authors: Malara
authors: Fabrizio
authors: F
authors: Vianello
authors: Alessandro
authors: A
authors: Pecci
authors: Raffaella
authors: R
authors: Scandellari
authors: Matteo
authors: M
authors: Floris
authors: Alessandra
authors: A
authors: Balduini
authors: Fabrizio
authors: F
authors: Fabris
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D001606:Bernard-Soulier Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005091:Exons / Q000235:genetics; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020125:Mutation, Missense; D019038:Platelet Glycoprotein GPIb-IX Complex; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D012333:RNA, Messenger; C094990:adhesion receptor