Variant screening of the RHD gene in a large cohort of subjects with D phenotype ambiguity: report of 17 novel rare alleles

Transfusion. 2012 Apr;52(4):759-64. doi: 10.1111/j.1537-2995.2011.03350.x. Epub 2011 Sep 26.

Abstract

Background: A considerable number of RHD alleles responsible for weak and partial D phenotypes have been identified over the past decade. Two particular concerns, namely, 1) that red blood cells of these phenotypes may cause anti-D immunization when transfused to D- recipients and 2) that serologic determination of these phenotypes is often doubtful, make genetic analysis of the RHD gene highly desirable.

Study design and methods: Blood samples that displayed D phenotype ambiguity (as determined by serologic analyses) were collected from several sites of the Etablissement Français du Sang and subjected to RHD variant screening by means of a previously established denaturing high-performance liquid chromatography method followed by direct sequencing.

Results: Systematic screening of the RHD coding sequences as well as the exon-intron boundaries identified DNA variants in 755 of the 806 samples analyzed. In particular, this resulted in the identification of 10 novel single-nucleotide substitutions and seven novel complex alleles.

Conclusion: This study further increased the already large repertoire of RHD allelic variants. Whereas most of the newly found variants are putative weak or partial D alleles, most of the complex alleles are readily understandable in the present phylogenetic model of RHD.

MeSH terms

  • 3' Untranslated Regions
  • Alleles*
  • Cohort Studies
  • Genetic Variation
  • Humans
  • Phenotype
  • Prospective Studies
  • Rh-Hr Blood-Group System / genetics*
  • Rh-Hr Blood-Group System / immunology

Substances

  • 3' Untranslated Regions
  • Rh-Hr Blood-Group System
  • Rho(D) antigen