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Amino acid 489 is encoded by a mutational "hot spot" on the beta 3 integrin
chain: the CA/TU human platelet alloantigen system
R Wang, JG McFarland, R Kekomaki and PJ Newman
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee
53233.
A new platelet alloantigen, termed CA, has recently been implicated in a
case of neonatal alloimmune thrombocytopenia (NATP) in a Filipino family in
Canada. Maternal anti-CA serum reacted with glycoprotein (GP) IIIa and
maintained its reactivity after removal of high mannose carbohydrate
residues from GPIIIa. The monoclonal antibody (MoAb) AP3 partially blocked
binding of anti-CA to GPIIIa, suggesting that the CA polymorphism is
proximal to the AP3 epitope. Platelet RNA polymerase chain reaction (PCR)
was used to amplify the region of GPIIIa cDNA that encodes this region of
the protein. DNA sequence analysis showed a G<==>A nucleotide
substitution at base 1564 that results in an arginine (Arg)
(CGG)<==>glutamine (Gln) (CAG) polymorphism in amino acid (AA) 489.
Further analysis of PCR-amplified genomic DNA from 27 normal individuals
showed that AA 489 is encoded by a mutational "hot spot" of the GPIIIa
gene, as three different codons for the wild-type Arg489 of GPIIIa were
also found. The codon usage for Arg489 was found to be: CGG (63%), CGA
(37%), and CGC (< 1%). These frequency data were valuable in determining
the relationship of the CA alloantigen to the serologically defined TU
GPIIIa polymorphism that is present in low frequency in the Finish
population. Analyses of PCR-amplified genomic DNA showed the CA and TU
alloantigens to be identical at the molecular level. Definition of these
new molecular variants of the beta 3 integrin chain should prove valuable
in the diagnosis of NATP in these two geographically disparate populations,
and it may also provide useful genetic markers for examining other
pathologic variations of the GPIIb-IIIa complex.
Volume 82,
Issue 11,
pp. 3386-3391,
12/01/1993
Copyright © 1993 by The American Society of Hematology
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