The low-incidence MNS antigens M^v, s^D, and Mit arise from single amino acid substitutions on GPB

BACKGROUND: GPB carries 'N' at its N-terminus and S and s, determined by a polymorphism at amino acid position 29 (Met29Thr). The low-incidence antigens Mv, sD, and Mit are associated with weakened expression of S and/or s, and the purpose of this study was to define their molecular bases. METHODS: The GPB gene (GYPB) was sequenced after RT-PCR of RNA from four samples: two Mv+, one sD+, and one Mit+. The point mutations observed were confirmed by sequencing of genomic DNA from these and other examples of sD+ and Mit+ samples. RESULTS: A point mutation of 65C>G observed in the Mv+ samples predicted a change of Thr3Ser. A mutation of C>G at nucleotide 173 of the GYPB coding sequence, observed in two sD+ samples, predicted a change of Pro39Arg. Three Mit+ samples showed a nucleotide substitution of 161G>A, which predicted a change of Arg35His. Altered expression of S or s was confirmed by serologic tests. CONCLUSION: These results confirm that Arg35 is important for full expression of S. Pro39 and, surprisingly, Thr3 are also important for full expression of s. Furthermore, Thr3 must be essential for expression of 'N,' as Mv+ RBCs lack 'N'.