A novel Phe171Cys mutation in integrin alpha causes Glanzmann thrombasthenia by abrogating alphabeta complex formation

Journal of Thrombosis and Haemostasis : JTH
N RosenbergUri Seligsohn

Abstract

Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterized by lack of platelet aggregation induced by most agonists. The disease is caused by mutations in either alpha(IIb)[glycoprotein (GP) IIb] or beta(3) (GPIIIa) genes that lead to a lack or dysfunction of the integrin alpha(IIb)beta(3) which serves as a fibrinogen receptor. Mucocutaneous bleeding manifestations and platelet dysfunction consistent with GT were observed in three members of a Cypriot family: a 3-year-old proband, her father and her paternal uncle. To determine the molecular basis of GT in this family and to characterize possible biochemical and structural defects. Analysis of the patients' platelets by fluorescence-activated cell sorting demonstrated trace amounts of beta(3), no alpha(IIb) and no alpha(IIb)beta(3) on the membrane. Sequence analysis revealed a novel T607G transversion in exon 5 of the alpha(IIb) gene predicting a Phe171Cys alteration that created a PstI recognition site. All three patients were homozygous for the mutation, the mother and paternal grandparents of the proband were heterozygous, whereas 110 healthy subjects lacked this transversion. Chinese hamster ovary cells cotransfected with cDNAs of mutated alpha(...Continue Reading

References

Jun 1, 1987·The Journal of Cell Biology·A DuperrayG Marguerie
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Jun 1, 1996·Current Opinion in Structural Biology·S R Eddy
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Jan 1, 1997·Methods in Enzymology·E A Merritt, D J Bacon

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Citations

Aug 2, 2006·Journal of Thrombosis and Haemostasis : JTH·E J R NelsonA Srivastava
Sep 10, 2017·European Journal of Haematology·Rungnapa IttiwutKanya Suphapeetiporn
Jan 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vineet GuptaM Amin Arnaout

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