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A novel nonsense variant in RHAG underlies a Nordic Rhnull phenotype.

Hellberg, Åsa LU ; Arsenovic, Mirjana Grujic ; Sørvoll, Ingvild Hausberg ; Lubenow, Norbert ; Sareneva, Inna ; Haimila, Katri ; Nordström, Magnus ; Olsson, Martin L LU orcid and Storry, Jill R LU (2023) In Vox Sanguinis 118(8). p.690-694
Abstract

BACKGROUND AND OBJECTIVES: The extremely rare Rh
null 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. Rh
null cells have altered expression of glycophorin B and LW glycoprotein.

MATERIALS AND METHODS: Four unrelated Rh
null 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... (More)

BACKGROUND AND OBJECTIVES: The extremely rare Rh
null 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. Rh
null cells have altered expression of glycophorin B and LW glycoprotein.

MATERIALS AND METHODS: Four unrelated Rh
null 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 Rh
null allele was identified. In addition, it was shown that s+ Rh
null red blood cells are not only U- but also have qualitative changes in their s antigen expression.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Vox Sanguinis
volume
118
issue
8
pages
690 - 694
publisher
Wiley-Blackwell
external identifiers
  • scopus:85161408202
  • pmid:37265146
ISSN
1423-0410
DOI
10.1111/vox.13478
language
English
LU publication?
yes
additional info
© 2023 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.
id
5242e9e3-e449-4960-a7d1-5d4e291522fd
date added to LUP
2023-07-10 15:10:44
date last changed
2024-04-19 23:17:24
@article{5242e9e3-e449-4960-a7d1-5d4e291522fd,
  abstract     = {{<p>BACKGROUND AND OBJECTIVES: The extremely rare Rh<br>
 null 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. Rh<br>
 null cells have altered expression of glycophorin B and LW glycoprotein.<br>
 </p><p>MATERIALS AND METHODS: Four unrelated Rh<br>
 null 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.<br>
 </p><p>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&gt;g in all samples. RHD/RHCE showed no alterations.</p><p>CONCLUSION: A novel Nordic Rh<br>
 null allele was identified. In addition, it was shown that s+ Rh<br>
 null red blood cells are not only U- but also have qualitative changes in their s antigen expression.<br>
 </p>}},
  author       = {{Hellberg, Åsa and Arsenovic, Mirjana Grujic and Sørvoll, Ingvild Hausberg and Lubenow, Norbert and Sareneva, Inna and Haimila, Katri and Nordström, Magnus and Olsson, Martin L and Storry, Jill R}},
  issn         = {{1423-0410}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{8}},
  pages        = {{690--694}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Vox Sanguinis}},
  title        = {{A novel nonsense variant in RHAG underlies a Nordic Rh<sub>null</sub> phenotype.}},
  url          = {{http://dx.doi.org/10.1111/vox.13478}},
  doi          = {{10.1111/vox.13478}},
  volume       = {{118}},
  year         = {{2023}},
}