A NEW HIGH-MOLECULAR-WEIGHT GLYCOPHORIN-C VARIANT WITH A DUPLICATION OF EXON-2 IN THE GLYCOPHORIN-C GENE

Glycophorin C (GPC) and glycophorin D (GPD) are closely related sialog lycoproteins in the human red blood cell (RBC) membrane. Both are thou ght to be encoded by the GPC gene (GYPC). We report here the new GPC v ariant, MAT, with a high-molecular-weight form of GPC and GPD. The mur ine monoclonal antibody to GPC (CBC-96), which had specificity for the N-terminal region of GPC, gave a stronger reactivity with the MAT RBC s than did normal RBCs in direct agglutination tests. Immunoblotting o f the MAT RBC membranes with anti-GPC antibodies showed the apparent m olecular weight of GPC.MAT and GPD.MAT was 5000 greater than that of t heir normal counterparts. cDNA was synthesized from total RNA obtained from three unrelated, heterozygous MAT blood donors and analysed by t he polymerase chain reaction with primers that spanned sequences encod ed by GYPC. Two fragments were generated: one was 510 bp, the other wa s 453 bp and corresponded to the normal GPC. Sequencing of the mutant 510-bp fragment showed an insert of 57 nucleotides that corresponds to the entire sequence of exon 2 in GYPC. These results show that MAT is the result of a duplication of exon 2 in GYPC, which probably encodes the two high-molecular weight forms GPC.MAT and GPD.MAT. The MAT muta tion is found with a frequency of 0.02% in the Japanese population.