Single amino acid substitution in human platelet glycoprotein Ibβ is responsible for the formation of the platelet-specific alloantigen Iya

Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1849-1855 ◽  
Author(s):  
Ulrich J. H. Sachs ◽  
Volker Kiefel ◽  
Micaela Böhringer ◽  
Vahid Afshar-Kharghan ◽  
Hartmut Kroll ◽  
...  

We recently described a new low-frequency platelet alloantigen on the human platelet glycoprotein (GP) Ib-IX complex, termed Iya, which was implicated in a severe case of neonatal alloimmune thrombocytopenia. Immunoprecipitation studies with trypsin-treated platelets indicated that the Iyaalloantigenic determinants are formed by the membrane-associated remnant moiety of GP Ib (GP Ibr) together with GP Ibβ and GP IX. To elucidate the molecular basis underlying the Iya alloantigen, we amplifiedGPIbr, GPIbβ, andGPIX genes by polymerase chain reaction (PCR). Nucleotide-sequence analysis of these 3 genes showed a G to A transition at position 141 on GPIbβ gene in a subject positive for Iya. This transition resulted in a Gly15Glu dimorphism on the N-terminal domain ofGPIbβ. This finding was confirmed by genotyping analysis of 6 Iya-positive subjects by restriction fragment length polymorphism (RFLP) studies using NarI endonuclease. In 300 randomly selected healthy blood donors, one Iya-positive individual was found. Phenotypes determined by monoclonal antibody-specific immobilization of platelet antigens assay and genotypes determined by RFLP were identical in this population. Analysis of Iya-positive platelets showed that the point mutation affected neither the degree of surface expression nor the function of the GP Ib-GP Ibβ-IX complex on the platelet surface. Transient expression of the GP Ib-IX complex in CHO cells using wild-type GP Ibβ (Gly15) or mutant GP Ibβ (Glu15) allowed us to demonstrate that this single amino acid substitution is sufficient to induce Iya epitope(s).

1996 ◽  
Vol 5 (3) ◽  
pp. 542-545 ◽  
Author(s):  
Kunihiko Gekko ◽  
Youjiro Tamura ◽  
Eiji Ohmae ◽  
Hideyuki Hayashi ◽  
Hiroyuki Kagamiyama ◽  
...  

Microbiology ◽  
2015 ◽  
Vol 161 (4) ◽  
pp. 895-902 ◽  
Author(s):  
Mouparna Dutta ◽  
Debasish Kar ◽  
Ankita Bansal ◽  
Sandeep Chakraborty ◽  
Anindya S. Ghosh

1993 ◽  
Vol 30 (18) ◽  
pp. 1671-1677 ◽  
Author(s):  
Krishna V. Kesari ◽  
Grada van Bleek ◽  
Stanley G. Nathenson ◽  
Jan Geliebter

PEDIATRICS ◽  
1989 ◽  
Vol 83 (5) ◽  
pp. 734-736
Author(s):  
John R. Priest ◽  
Jan Watterson ◽  
Richard T. Jones ◽  
Anne E. Faassen ◽  
Bo E. Hedlund

A well but cyanotic newborn was found to have a mutant γ-globin chain, leading to a functionally abnormal fetal hemoglobin. A single amino acid substitution was found in a site consistent with known adult M hemoglobins. This patient showed no clinical evidence of cyanosis at 5 weeks of age as γ-chain synthesis was replaced by β-chain synthesis. A sibling born 20 months later was also cyanotic and the same mutant hemoglobin was found.


Sign in / Sign up

Export Citation Format

Share Document