RhD variant caused by an in-frame triplet duplication in the RHD gene

Transfusion. 2011 Mar;51(3):570-3. doi: 10.1111/j.1537-2995.2010.02856.x. Epub 2010 Aug 24.


Background: The RHD gene is highly polymorphic and a large number of D variants have already been detected. Several mechanisms are involved in the origin of D variants. In-frame deletions, resulting in a single-amino-acid deletion, have been described associated with RhD and RhCE variants. No in-frame duplications and/or insertions have been reported in the RH genes to date.

Study design and methods: Blood samples from a Brazilian blood donor and his sister were serologically tested with routine anti-D reagents and anti-D panels (ALBAclone advanced partial D typing kit, Alba Bioscience Limited; and D-Screen, Diagast), followed by molecular biology techniques, RHD polymerase chain reaction with sequence-specific priming and sequencing.

Results: Samples tested negative with routine immunoglobulin M (IgM) anti-D reagents and positive with IgG anti-D, which detect weak D cells. The pattern of results with anti-D panels did not correspond to any described before. A 3-bp in-frame duplication within Exon 1 (c.75_77dupTCT), resulting in the duplication of leucine 26 (p.Leu26dup), was identified in the two samples.

Conclusion: We report the first RhD variant associated with a 3-bp in-frame duplication in the RHD gene, predicted to be located within the RhD protein transmembrane domain that might be expected to result in a weak-D-like phenotype, concordant with serologic findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exons
  • Gene Duplication*
  • Genetic Variation
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Rh-Hr Blood-Group System / genetics*
  • Rh-Hr Blood-Group System / immunology


  • Immunoglobulin G
  • Immunoglobulin M
  • Rh-Hr Blood-Group System
  • Rho(D) antigen