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. 2023 Aug;118(8):690-694.
doi: 10.1111/vox.13478. Epub 2023 Jun 2.

A novel nonsense variant in RHAG underlies a Nordic Rhnull phenotype

Åsa Hellberg  1 , Mirjana Grujic Arsenovic  2 , Ingvild Hausberg Sørvoll  2 , Norbert Lubenow  3 , Inna Sareneva  4 , Katri Haimila  4 , Magnus Nordström  5 , Martin L Olsson  1   6 , Jill R Storry  1   6
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A novel nonsense variant in RHAG underlies a Nordic Rhnull phenotype

Åsa Hellberg et al. Vox Sang. 2023 Aug.

Abstract

Background and objectives: The extremely rare Rhnull phenotype is characterized by the absence of all Rh antigens on erythrocytes. It is divided into the regulator and amorph types based on the underlying genetic background. The more common regulator type depends on critical variants silencing RHAG, which encodes RhAG glycoprotein, necessary for RhD/RhCE expression. Rhnull cells have altered expression of glycophorin B and LW glycoprotein.

Materials and methods: Four unrelated Rhnull individuals were investigated. Serological testing was performed according to standard blood bank practice. RHD/RHCE and S/s allele-specific Polymerase chain reaction (PCR) genotyping was done on genomic DNA using in-house PCR assays. RHAG, and in some cases also RHD/RHCE, were sequenced. Initial s phenotyping results triggered additional serological investigation.

Results: Anti-Rh29 was identified in all four individuals. Extended typing with anti-S and anti-s showed that the three samples predicted to type as s+ failed to react with 2 of 5 anti-s. Sequence analysis of all 10 RHAG exons and the immediate intron/exon boundaries revealed a single nucleotide variant in the 3'-end of intron 6, c.946 -2a>g in all samples. RHD/RHCE showed no alterations.

Conclusion: A novel Nordic Rhnull allele was identified. In addition, it was shown that s+ Rhnull red blood cells are not only U- but also have qualitative changes in their s antigen expression.

Keywords: RHAG; Rh blood group system; Rhnull; S−s− phenotype.

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References

REFERENCES

    1. Avent ND, Madgett TE, Lee ZE, Head DJ, Maddocks DG, Skinner LH. Molecular biology of Rh proteins and relevance to molecular medicine. Expert Rev Mol Med. 2006;8:1-20.
    1. Daniels G. Human blood groups. 3rd ed. Oxford: Wiley-Blackwell; 2013.
    1. Arsenovic MG, Grimsley S, Hausberg Sørvoll I, McNeill A, Titze T, Husebekk A, et al. The Rhnull phenotype in a Norwegian family is due to a novel RHAG mutation. Vox Sang. 2014;107:192.
    1. Sistonen P, Palosuo T, Snellman A. Identical twins with the Rhnull phenotype of the regulator type in a Finnish Lapp family. Vox Sang. 1985;48:174-7.
    1. Cherif-Zahar B, Raynal V, Gane P, Mattei MG, Bailly P, Gibbs B, et al. Candidate gene acting as a suppressor of the RH locus in most cases of Rh-deficiency. Nat Gen. 1996;12:168-73.

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