Two large deletions extending beyond either end of the RHD gene and their red cell phenotypes

J Hum Genet. 2018 Jan;63(1):27-35. doi: 10.1038/s10038-017-0345-3. Epub 2017 Nov 16.


Only two partial deletions longer than 655 nucleotides had been reported for the RHD gene, constrained within the gene and causing DEL phenotypes. Using a combination of quantitative PCR and long-range PCR, we examined three distinct deletions affecting parts of the RHD gene in three blood donors. Their RHD nucleotide sequences and exact boundaries of the breakpoint regions were determined. DEL phenotypes were caused by a novel 18.4 kb deletion and a previously published 5.4 kb deletion of the RHD gene; a D-negative phenotype was caused by a novel 7.6 kb deletion. Examination of the deletion-flanking regions suggested microhomology-mediated end-joining, replication slippage, and non-homologous end-joining, respectively, as the most likely mechanisms for the three distinct deletions. We described two new deletions affecting parts of the RHD gene, much longer than any previously reported partial deletion: one was the first deletion observed at the 5' end of the RHD gene extending into the intergenic region, and the other the second deletion observed at its 3' end. Large deletions present at either end are a mechanism for a much reduced RhD protein expression or its complete loss. Exact molecular characterization of such deletions is instrumental for accurate RHD genotyping.

MeSH terms

  • Base Sequence*
  • DNA, Intergenic* / genetics
  • DNA, Intergenic* / metabolism
  • Erythrocytes / cytology
  • Erythrocytes / metabolism*
  • Female
  • Gene Expression Regulation / genetics*
  • Humans
  • Male
  • Rh-Hr Blood-Group System* / biosynthesis
  • Rh-Hr Blood-Group System* / genetics
  • Sequence Deletion*


  • DNA, Intergenic
  • Rh-Hr Blood-Group System
  • Rho(D) antigen