title: Molecular basis of weak D phenotypes.
abstract: A Rhesus D (RhD) red blood cell phenotype with a weak expression of the D antigen occurs in 0.2% to 1% of whites and is called weak D, formerly Du. Red blood cells of weak D phenotype have a much reduced number of presumably complete D antigens that were repeatedly reported to carry the amino acid sequence of the regular RhD protein. The molecular cause of weak D was unknown. To evaluate the molecular cause of weak D, we devised a method to sequence all 10 RHD exons. Among weak D samples, we found a total of 16 different molecular weak D types plus two alleles characteristic of partial D. The amino acid substitutions of weak D types were located in intracellular and transmembraneous protein segments and clustered in four regions of the protein (amino acid positions 2 to 13, around 149, 179 to 225, and 267 to 397). Based on sequencing, polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction using sequence-specific priming, none of 161 weak D samples investigated showed a normal RHD exon sequence. We concluded, that in contrast to the current published dogma most, if not all, weak D phenotypes carry altered RhD proteins, suggesting a causal relationship. Our results showed means to specifically detect and to classify weak D. The genotyping of weak D may guide Rhesus negative transfusion policy for such molecular weak D types that were prone to develop anti-D.
authors.affiliation: Abteilung Transfusionsmedizin, Universitätsklinikum Ulm and DRK-Blutspendedienst Baden-Württemberg, Institut Ulm, Ulm, Germany.
authors.forename: F F
authors.initials: FF
authors.lastname: Wagner
authors.forename: C
authors.initials: C
authors.lastname: Gassner
authors.forename: T H
authors.initials: TH
authors.lastname: Müller
authors.forename: D
authors.initials: D
authors.lastname: Schönitzer
authors.forename: F
authors.initials: F
authors.lastname: Schunter
authors.forename: W A
authors.initials: WA
authors.lastname: Flegel
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D020125:Mutation, Missense; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic; D012204:Rh-Hr Blood-Group System / Q000737:chemistry* / Q000235:genetics*
chemical_list: D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen