Novel intronic RHD variants identified in serologically D‐negative blood donors

Abstract

All identified RHD variants contain at least one mutation that probably affects splicing to generate D-negative phenotype. Hence, ethnic RhD antigen background must be considered when developing transfusion and obstetric strategies.

RHD Genotypes in a Chinese Cohort of Pregnant Women

“…More than 300 variant alleles of RHD have been reported ( Kawano et al, 1998 ; Ye et al, 2007 ; Fichou et al, 2015 ; Chen et al, 2016 ; Ogasawara et al, 2016 ; El Wafi et al, 2017 ; Chun et al, 2018 ; Raud et al, 2019 ), including single-nucleotide polymorphisms (SNPs), small or large fragment deletions, gene rearrangements, and complete RHD deletions. The intron mutation disrupts a constitutive splice site, resulting in improper retention of an intron or activation of a cryptic splice site in the vicinity of the mutant.…”

“…Furthermore, lacking fresh blood samples for RNA extraction, many functional studies mainly relied on recombinant plasmids. Hence, clinical transcriptome data and protein analysis are urgently needed to investigate genotype-phenotype mechanisms ( Liu et al, 2010 ; Fichou et al, 2015 ; El Wafi et al, 2017 ).…”

“…However, few studies get insights into the mRNA product of RHD variations in China ( Liu et al, 2010 ). Moreover, Most RHD variants studies rely on the bioinformatics tools in silico and plasmid construct ( Fichou et al, 2015 ; El Wafi et al, 2017 ). Very little functional data under physiological conditions is available to characterize the effect of the mutation at the molecular level.…”

<p>Potential of next-generation sequencing to match blood group antigens for transfusion</p>

“…Recent studies have confirmed NGS effectiveness in resolving the molecular background of orphan antigens with an as yet unknown genetic basis. [49][50][51][52][53][54][55][56][57][58][59] The WES strategy based on genomic DNA from patients with detected antibodies and their relatives combined with appropriate variant filtering have revealed one SNV in the GYPA gene. 49 This discovery allowed the SARA antigen to join the MNS blood group system.…”

“…In a group of RhD negative individuals, El Wafi et al revealed five novel intronic RHD variants that probably affected the splicing of D protein. 59 Moller et al analyzed the genomic sequences of genes encoding 36 blood group systems from over 2500 individuals enrolled in the 1000 Genome Projects. 32 The study revealed 1241 non-synonymous variants.…”