The MNS blood group antigens, Vr (MNS12) and mts (MNS14), each arise from an amino acid substitution on glycophorin A

Background and Objectives: The antigens, Vr (MNS12) and Mt(a) (MNS14), are low-incidence antigens of the MNS blood group system. The Vr antigen has be en found only on the red blood cells (RBCs) of persons of Dutch ancestry wh ereas the Mta antigen has been found on the RBCs of persons from a wide geo graphic distribution. The objective of this study was to determine the mole cular basis of Vr and Mt(a). Materials and Methods: Following RT-PCR amplif ication of total RNA isolated from one Vr+ person (G488) and one Mt(a+) per son (GH), the genes encoding glycophorin A (GYPA) and glycophorin B (GYPB) were cloned and sequenced. To confirm the point mutation observed in the cD NA from G488 (Vr+), GYPA exon 3 was cloned and sequenced from the genomic D NA of G488 and a second unrelated Vr+ person (MU). A restriction fragment l ength polymorphism (RFLP) assay was used to analyze genomic DNA from 11 Mt( a+) persons (10 unrelated) following PCR amplification of GYPA exon 3. Resu lts: The coding sequence of GYPB was normal in both G488 (Vr+) and GH (Mt(a +)), Sequencing data from GYPA clones derived from G488 showed to full leng th GYPA sequences: A normal GYPA M allele and a GYPA M allele with a point mutation 197C-->A. Sequencing of GYPA exon 3 from G488 and MU confirmed the point mutation. Sequencing data drom GYPA clones derived from GH showed tw o full length GYPA sequences: a normal GYPA NI allele and a GYPA N allele w ith a point mutation 230C-->T. RFLP analysis based on the point mutation sh owed that DNA from 11 Mt(a+) samples were heterozygous for the point mutati on. Conclusion: The Vr antigen arises from a point mutation 197C-->A on GYP A which is predicted to change serine at position 47 to tyrosine. This chan ge introduces a new cr-chymotrypsin cleavage site. The Mt(a) antigen arises from a point mutation 230C-->T which is predicted to change threonine at p osition 58 to isoleucine. Copyright (C) 2000 S. Karger AG, Basel.