title: Frequency and characterization of known and novel RHD variant alleles in 37 782 Dutch D-negative pregnant women.
abstract: To guide anti-D prophylaxis, Dutch D- pregnant women are offered a quantitative fetal-RHD-genotyping assay to determine the RHD status of their fetus. This allowed us to determine the frequency of different maternal RHD variants in 37 782 serologically D- pregnant women. A variant allele is present in at least 0·96% of Dutch D- pregnant women The D- serology could be confirmed after further serological testing in only 54% of these women, which emphasizes the potential relevance of genotyping of blood donors. 43 different RHD variant alleles were detected, including 15 novel alleles (11 null-, 2 partial D- and 2 DEL-alleles). Of those novel null alleles, one allele contained a single missense mutation (RHD*443C>G) and one allele had a single amino acid deletion (RHD*424_426del). The D- phenotype was confirmed by transduction of human D- erythroblasts, consolidating that, for the first time, a single amino acid change or deletion causes the D- phenotype. Transduction also confirmed the phenotypes for the two new variant DEL-alleles (RHD*721A>C and RHD*884T>C) and the novel partial RHD*492C>A allele. Notably, in three additional cases the DEL phenotype was observed but sequencing of the coding sequence, flanking introns and promoter region revealed an apparently wild-type RHD allele without mutations.
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tamara C
authors.initials: TC
authors.lastname: Stegmann
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Sanquin Diagnostic Services, Amsterdam, The Netherlands.
authors.forename: Barbera
authors.initials: B
authors.lastname: Veldhuisen
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Renate
authors.initials: R
authors.lastname: Bijman
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Florentine F
authors.initials: FF
authors.lastname: Thurik
authors.affiliation: Sanquin Diagnostic Services, Amsterdam, The Netherlands.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Bossers
authors.affiliation: Sanquin Diagnostic Services, Amsterdam, The Netherlands.
authors.forename: Goedele
authors.initials: G
authors.lastname: Cheroutre
authors.affiliation: Sanquin Diagnostic Services, Amsterdam, The Netherlands.
authors.forename: Remco
authors.initials: R
authors.lastname: Jonkers
authors.affiliation: Sanquin Diagnostic Services, Amsterdam, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Ligthart
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Sanquin Diagnostic Services, Amsterdam, The Netherlands.
authors.forename: Masja
authors.initials: M
authors.lastname: de Haas
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lonneke
authors.initials: L
authors.lastname: Haer-Wigman
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: C Ellen
authors.initials: CE
authors.lastname: van der Schoot
mesh_terms: D000483:Alleles; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D009154:Mutation; D009426:Netherlands; D010641:Phenotype; D011247:Pregnancy; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D018029:Rho(D) Immune Globulin / Q000235:genetics*
chemical_list: C061961:RHO(D) antibody; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin
keywords: D- phenotype; RHD variant alleles; Rh blood group; blood group genotyping