Serologic and molecular investigations of DAR1 (weak D Type 4.2), DAR1.2, DAR1.3, DAR2 (DARE), and DARA

Transfusion. 2013 Nov;53(11 Suppl 2):3000-8. doi: 10.1111/trf.12363. Epub 2013 Jul 31.

Abstract

Background: The partial D variant DAR1 (weak D Type 4.2) is caused by three single-point mutations, 602C>G, 667T>G, and 1025T>C. Here we report a molecular study on different D variants belonging to the DAR category (DAR1, DAR1.2, DAR1.3, and DAR2) and their serologic data.

Study design and methods: A total of 42 samples belonging to the DAR category were screened for the presence of the silent mutations 744C>T and 957G>A. The samples were phenotyped for RhD and RhCE, characterized for RhD epitope expression, and sequenced for RHD exons. Flow cytometry was performed to determine RhD antigen density.

Results: The silent mutation 744C>T was found in all six samples previously typed as RHD*DAR2 (602C>G, 667T>G, 957G>A, 1025T>C). In addition to the three nucleotide changes originally reported for the RHD*DAR1 allele, the silent mutations 744C>T and 957G>A were found in 14 of 16 samples previously typed as RHD*DAR1. In the remaining two samples one additional silent mutation, 744C>T, was found. Serologically the DAR1.2 and DAR1.3 samples analyzed in this study showed no distinct difference in their anti-D reaction pattern compared to each other. The anti-D reaction pattern of DARA/DAR2 showed some distinct differences compared to those of DAR1.2 and DAR1.3.

Conclusion: RHD*DARA and RHD*DAR2 are the same allele. Furthermore, the alleles RHD*DAR1.2 and RHD*DAR1.3 both exist; however, the silent mutation 957G>A (V319) showed no influence on the RhD phenotype.

MeSH terms

  • Alleles
  • Amino Acid Substitution / genetics
  • Blood Grouping and Crossmatching / methods
  • Flow Cytometry
  • Humans
  • Isoantibodies / immunology
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Rh-Hr Blood-Group System / classification
  • Rh-Hr Blood-Group System / genetics*
  • Rh-Hr Blood-Group System / immunology
  • Rh-Hr Blood-Group System / metabolism
  • Rho(D) Immune Globulin
  • Sequence Analysis, DNA
  • Serologic Tests

Substances

  • Isoantibodies
  • RHO(D) antibody
  • Rh-Hr Blood-Group System
  • Rho(D) Immune Globulin
  • Rho(D) antigen