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MNS blood group system contains 49 recognized antigens; the major antigens are M, N, S, s, and U. M and N antigens are located on glycophorin A (GPA), while S, s, and U antigens are carried on glycophorin B (GPB). Both are single-pass membrane sialoglycoproteins ( Fig. 28.1 ). Genes encoding GPA and GPB are adjacent on the chromosome, and inheritance of MN and Ss antigens are linked ( Table 28.1 ).
Phenotype | Prevalence (%) | |
---|---|---|
White | Black | |
M+ N− S+ s− | 6 | 2 |
M+ N− S+ s+ | 14 | 7 |
M+ N− S− s+ | 10 | 16 |
M+ N+ S+ s− | 4 | 2 |
M+ N+ S+ s+ | 22 | 13 |
M+ N+ S− s+ | 23 | 33 |
M− N+ S+ s− | 1 | 2 |
M− N+ S+ s+ | 6 | 5 |
M− N+ S− s+ | 15 | 19 |
M+ N− S− s− | 0 | 0.4 |
M+ N+ S− s− | 0 | 0.4 |
M− N+ S− s− | 0 | 0.7 |
M and N antigens are antithetical and sensitive to enzyme treatment including ficin, papain, trypsin, and pronase; these properties can aid in antibody identification. The null phenotype lacks M, N, and high-prevalence antigen(s) and is designated En(a−).
The antithetical S and s antigens are sensitive to α-chymotrypsin and pronase, with variable sensitivity to ficin and papain. U is a high-prevalence antigen on GYB. RBCs with U− or U VAR (U weak) phenotypes are S− and s− and are found in blacks with approximate frequency of 1.5%. The glycophorin (GYP) null phenotype, designated M k M k , lacks both MN and Ss antigens.
GPA is a receptor for bacteria, viruses, and Plasmodium falciparum , a chaperone for Band 3 transport to the RBC membrane, a major component contributing to the negatively charged RBC glycocalyx, and may also function as a complement regulator. GPB is a member of the Band 3/Rh-macrocomplex in the RBC membrane. The rare null phenotypes are not associated with any apparent health defects.
GPA and GPB are encoded by GYPA and GYPB located in close proximity on chromosome 4. The M/N-encoding alleles are designated GYPA ∗ M or GYPA ∗ N and differ by three nucleotide changes in exon 2 (c.59C>T; c.71G>A; c.72T>G), which encode two amino acid changes (p.Ser20Leu and p.Gly24Glu). The S/s alleles are GYPB ∗ S and GYPB ∗ s and differ by one change in exon 4 (c.143C>T; p.Thr48Met). The U− phenotype is caused by deletion of the coding region of GYPB , while the U VAR (U weak) phenotype is associated with partial or complete skipping of exon 5. Most of the low-frequency antigens result from either amino acid substitutions or rearrangements between the two homologous genes giving rise to hybrid alleles.
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