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Journal Articles Transfusion Year : 2012

Weak D caused by a founder deletion in the RHD gene.

Y. Fichou
  • Function : Author
J.-M. Chen
  • Function : Author
Maréchal C. Le
  • Function : Author
Dominique Jamet
I. Dupont
  • Function : Author
C. Chuteau
  • Function : Author
M.-J. Loirat
  • Function : Author
C. Férec
  • Function : Author


BACKGROUND: The RhD blood group system exemplifies a genotype-phenotype correlation by virtue of its highly polymorphic and immunogenic nature. Weak D phenotypes are generally thought to result from missense mutations leading to quantitative change of the D antigen in the red blood cell membrane or intracellularly. STUDY DESIGN AND METHODS: Different sets of polymerase chain reaction primers were designed to map and clone a deletion involving RHD Exon 10, which was found in approximately 3% of approximately 2000 RHD hemizygous subjects with D phenotype ambiguity. D antigen density was measured by flow cytometry. Transcript analysis was carried out by 3'-rapid amplification of complementary DNA ends. Haplotype analysis was performed by microsatellite genotyping. RESULTS: A 5405-bp deletion that removed nearly two-thirds of Intron 9 and almost all of Exon 10 of the RHD gene was characterized. It is predicted to result in the replacement of the last eight amino acids of the wild-type RhD protein by another four amino acids. The mean RhD antigen density from two deletion carriers was determined to be only 30. A consensus haplotype could be deduced from the deletion carriers based on the microsatellite genotyping data. CONCLUSION: The currently reported deletion was derived from a common founder. This deletion appears to represent not only the first large deletion associated with weak D but also the weakest of weak D alleles so far reported. This highly unusual genotype-phenotype relationship may be attributable to the additive effect of three distinct mechanisms that affect mRNA formation, mRNA stability, and RhD/ankyrin-R interaction, respectively.


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hal-00702172 , version 1 (29-05-2012)



Y. Fichou, J.-M. Chen, Maréchal C. Le, Dominique Jamet, I. Dupont, et al.. Weak D caused by a founder deletion in the RHD gene.. Transfusion, 2012, ⟨10.1111/j.1537-2995.2012.03606.x⟩. ⟨hal-00702172⟩
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