Frequency and characterization of known and novel RHD variant alleles in 37 782 Dutch D-negative pregnant women.

Autor: Stegmann TC; Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Veldhuisen B; Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.; Sanquin Diagnostic Services, Amsterdam, The Netherlands., Bijman R; Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Thurik FF; Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Bossers B; Sanquin Diagnostic Services, Amsterdam, The Netherlands., Cheroutre G; Sanquin Diagnostic Services, Amsterdam, The Netherlands., Jonkers R; Sanquin Diagnostic Services, Amsterdam, The Netherlands., Ligthart P; Sanquin Diagnostic Services, Amsterdam, The Netherlands., de Haas M; Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.; Sanquin Diagnostic Services, Amsterdam, The Netherlands., Haer-Wigman L; Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., van der Schoot CE; Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2016 May; Vol. 173 (3), pp. 469-79. Date of Electronic Publication: 2016 Mar 27.
DOI: 10.1111/bjh.13960
Abstrakt: 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.
(© 2016 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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