Frequency and characterization of known and novel RHD variant alleles in 37 782 Dutch D‐negative pregnant women |
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| Authors: | Renate Bijman Florentine F. Thurik Bernadette Bossers Goedele Cheroutre Remco Jonkers Peter Ligthart Masja de Haas C. Ellen van der Schoot |
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| Affiliation: | 1. Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;2. Sanquin Diagnostic Services, Amsterdam, The Netherlands |
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| 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. |
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| Keywords: | Rh blood group RHD variant alleles D‐ phenotype blood group genotyping |
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