title: Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations.
abstract: The glycoprotein VI (GPVI)/FcRgamma complex is a key receptor for platelet activation by collagen. We describe, for the first time, 2 genetic abnormalities in one patient. This 10-year-old girl presented ecchymoses since infancy, a prolonged bleeding time despite a normal platelet count and no antiplatelet antibodies. Collagen-induced platelet activation was null, whereas GPVI quantification by flow cytometry evidenced an incomplete deficiency. Immunoblotting showed an abnormal migration of residual GPVI, and no FcRgamma defect. GPVI DNA sequencing revealed (1) an R38C mutation in exon 3 of one allele and (2) an insertion of 5 nucleotides in exon 4 of the other allele, leading to a premature nonsense codon and absence of the corresponding mRNA. Introduction of the R38C mutation into recombinant GPVI-Fc resulted in abnormal protein migration and a loss of collagen binding. Thus, this composite genetic GPVI deficiency and dysfunction cause absence of platelet responses to collagen and a mild bleeding phenotype.
authors: Inserm, U698, Hôpital Bichat, Paris, France.
authors: Bénédicte
authors: B
authors: Dumont
authors: Dominique
authors: D
authors: Lasne
authors: Chantal
authors: C
authors: Rothschild
authors: Maxime
authors: M
authors: Bouabdelli
authors: Véronique
authors: V
authors: Ollivier
authors: Claire
authors: C
authors: Oudin
authors: Nadine
authors: N
authors: Ajzenberg
authors: Bernard
authors: B
authors: Grandchamp
authors: Martine
authors: M
authors: Jandrot-Perrus
mesh_terms: D000483:Alleles; D001792:Blood Platelets / Q000378:metabolism; D002648:Child; D003062:Codon; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D009154:Mutation; D010641:Phenotype; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism
chemical_list: D003062:Codon; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D011961:Receptors, Fc; C098341:platelet membrane glycoprotein VI; D003094:Collagen