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Frequency and characterization of known and novel RHD variant alleles in 37 782 Dutch D‐negative pregnant women
Author(s) -
Stegmann Tamara C.,
Veldhuisen Barbera,
Bijman Renate,
Thurik Florentine F.,
Bossers Bernadette,
Cheroutre Goedele,
Jonkers Remco,
Ligthart Peter,
Haas Masja,
HaerWigman Lonneke,
Schoot C. Ellen
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13960
Subject(s) - allele , genotyping , genetics , phenotype , biology , missense mutation , null allele , genotype , allele frequency , gene
Summary 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.