Novel RHD alleles with weak hemagglutination and genetic Exon 9 diversity: weak D Types 45.1, 75, and 76

Transfusion. 2013 Nov;53(11 Suppl 2):2954-9. doi: 10.1111/trf.12180. Epub 2013 Apr 3.

Abstract

Background: Molecular variant RHD allele analysis is best complemented by detailed characterization of the associated D phenotype.

Study design and methods: Variant D types were characterized using molecular typing, RHD sequencing, extended serologic D antigen investigations, and flow cytometric D antigen quantification.

Results: We discovered three novel weak D types termed weak D Types 45.1, 75, and 76 with RHD nucleotide substitutions coding for amino acid exchanges in predicted intracellular RhD polypeptide stretches; antigen densities of approximately 1.990, 900, and 240 D sites per red blood cell were found, respectively. Adsorption-elution technique-supported D epitope mapping of these three weak D types demonstrated the expression of all tested D epitopes. Initial molecular typing of the three investigated samples by RHD gene exon scanning polymerase chain reaction using sequence-specific priming yielded a negative reaction for A1193 located in RHD Exon 9 and could be explained by specific mutations for weak D Types 45.1 (C818T, G1195A), 75 (G1194C), and 76 (A1215C).

Conclusion: All novel weak D types expressed all tested D epitopes. It is of interest that for weak D Types 45.1, 75, and 76, similar alleles with a maximal divergence of one amino acid only, that is, weak D Types 45, 41, and 68, respectively, have been reported so far.

MeSH terms

  • Alleles
  • Blood Donors
  • Epitopes / genetics
  • Epitopes / immunology
  • Erythrocytes / immunology
  • Erythrocytes / metabolism
  • Exons / genetics*
  • Gene Dosage
  • Genetic Variation*
  • Hemagglutination / genetics
  • Hemagglutination Tests
  • Humans
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Rh-Hr Blood-Group System / classification
  • Rh-Hr Blood-Group System / genetics*
  • Rh-Hr Blood-Group System / immunology*
  • Serologic Tests

Substances

  • Epitopes
  • Rh-Hr Blood-Group System
  • Rho(D) antigen

Associated data

  • GENBANK/FR748224
  • GENBANK/FR748225
  • GENBANK/FR748226