Characterization of Novel RHD Allele Variants and Their Implications for Routine Blood Group Diagnostics

The Rh system, including the highly immunogenic D antigen, is one of the clinically most important blood group systems in transfusion medicine. Numerous alleles of the gene are associated with variant RhD phenotypes. In case of Rh incompatibility, some of them can induce hemolytic transfusion reacti...

Full description

Saved in:
Bibliographic Details
Published in:Biomedicines 2024-02, Vol.12 (2), p.456
Main Authors: Matzhold, Eva M, Bemelmans, Maria, Polin, Helene, Körmöczi, Günther F, Schönbacher, Marlies, Wagner, Thomas
Format: Article
Language:English
Subjects:
Alleles
Annealing
Antibodies
Antigens
Automation
Bioinformatics
Blood & organ donations
Blood groups
D antigen
Epitopes
Fetuses
Flow cytometry
Genes
Genetic testing
Genotyping
Haplotypes
Hemolytic disease
Immunogenicity
Monoclonal antibodies
Mutation
partial D
Phenotypes
Proteins
Rh diagnostics
Rh system
RHD allele
Rhesus blood group
Stop codon
Thermal cycling
weak D
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The Rh system, including the highly immunogenic D antigen, is one of the clinically most important blood group systems in transfusion medicine. Numerous alleles of the gene are associated with variant RhD phenotypes. In case of Rh incompatibility, some of them can induce hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. Thus, accurate blood group diagnostics are critical for safe transfusion therapy. We characterized phenotypes of four individuals revealing weakened D expression during routine pre-transfusion testing. Standard gel card matrix techniques with monoclonal and polyclonal anti-D antibodies were used for serological typing, complemented using D epitope and antigen density analysis. Genotyping employing PCR with sequence-specific primers, genomic and allele-specific Sanger sequencing and in silico protein analysis were performed. Four novel alleles associated with weak D or partial D phenotypes were identified. One of the mutations is predicted to disrupt the terminal stop codon and result in an elongated translation of the mutant D protein that phenotypically exhibits a loss of D epitopes. Furthermore, a hybrid gene formed with the homologue gene is described. The presented data enhances the understanding of the Rh system and may contribute to continued advances in blood group diagnostics.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines12020456