A NOVEL POLYMORPHISM IN GLYCOPROTEIN-IV (REPLACEMENT OF PROLINE-90 BYSERINE) PREDOMINATES IN SUBJECTS WITH PLATELET GPIV DEFICIENCY

To clarify the molecular basis of the deficiency of glycoprotein IV (G PIV) of the platelet surface, we analyzed GPIV cDNA synthesized from p latelet RNA of five unrelated Japanese subjects whose platelets did no t express GPIV We confirmed the presence of normal-sized GPIV mRNA in platelets from subjects with GPIV deficiency. The sequence of platelet GPIV cDNA from GPIV deficient subject showed three differences when c ompared with the published sequence; 1) a replacement of a 478CCT codo n for proline-90 by TCT for serine, 2) a four-base insertion in the 3' -noncoding region, and 3) a substitution of A for 79C in the 5'-noncod ing region. The replacement of Pro90 by Ser predominates in subjects w ith GPIV deficiency; that is, four out of five platelets with GPIV def iciency contained GPIV mRNA encoding GPIV(Ser-90), while all platelets from 17 GPIV positive subjects had GPIV mRNA encoding GPIV(Pro-90). T he sequence of platelet GPIV cDNA which did not encode GPIV(Ser-90) fr om a subject with GPIV deficiency revealed no abnormality in the codin g region. The four-base insertion in the 3'-noncoding region and the s ubstitution of A for 79C in the 5'-noncoding region seems to be unrela ted to the expression of GPIV. The substitution of Ser for Pro90 might alter the GPIV structure or impair GPIV biosynthesis, resulting in a lack of detectable GPIV. This hypothesis remains to be tested.