title: Weak D caused by a founder deletion in the RHD gene.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Etablissement Français du Sang (EFS)-Bretagne, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Fichou
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Chen
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Maréchal
authors.forename: Déborah
authors.initials: D
authors.lastname: Jamet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dupont
authors.forename: Claude
authors.initials: C
authors.lastname: Chuteau
authors.forename: Cécile
authors.initials: C
authors.lastname: Durousseau
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Loirat
authors.forename: Pascal
authors.initials: P
authors.lastname: Bailly
authors.forename: Claude
authors.initials: C
authors.lastname: Férec
mesh_terms: D004910:Erythrocyte Membrane / Q000502:physiology; D005091:Exons / Q000235:genetics; D005434:Flow Cytometry; D018703:Founder Effect; D017353:Gene Deletion; D056726:Genetic Association Studies / Q000379:methods*; D006239:Haplotypes; D006801:Humans; D016130:Immunophenotyping; D018895:Microsatellite Repeats / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D021141:Nucleic Acid Amplification Techniques; D016133:Polymerase Chain Reaction; D020871:RNA Stability / Q000235:genetics; D012204:Rh-Hr Blood-Group System / Q000097:blood* / Q000235:genetics*
chemical_list: D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen