Polymorphism of platelet glycoprotein Ib associated with variability of the 85-kDa macroglycopeptide region

Polymorphism of platelet membrane glycoprotein Ib (GP Ib) has been described in both normal and functionally abnormal platelets. In this report we have investigated the polymorphism in one Australian Caucasian family with normal platelet function in which the following phenotypes were found: father, BC; mother, CD; son, BC; and daughter, BD; thus establishing a genetic basis for this phenomenon. The daughter's phenotype BD is highly distinctive due to the double-band pattern obtained by gel analysis. Platelets from the daughter were digested with either trypsin or elastase and the GP Ib cleavage products were examined by immunoprecipitation with anti-GP Ib-IX complex monoclonal antibodies against each of the major tryptic domains. On the basis of these studies, we have determined that the GPIb polymorphism in this family resides in the 85-kDa, macroglycopeptide region of the alpha-chain of GP Ib and not in either the 45-kDa, N-terminal region of GP Ib alpha or the membrane-associated region of the complex.