A novel RHD allele, which is known as c.336T>G, has been identified in a Chinese blood donor during routine D typing that is performed among all potential blood donors.
Recognizing the clinical significance of the Rhesus (Rh) blood group system in disorders such as hemolytic disease of the fetus and newborn (HDFN), the researchers reported on the discovery of a unique RHD allele that harbors a c.336T>G missense mutation in an individual from the Chinese Han population. Findings from this analysis were published recently in the journal Transfusion.
To date, there have been a total of 56 Rh antigens identified. In fact, in the Rh blood group system, the D antigen, which is also called RH1, is actually part of the RhD protein that is encoded by RHD. “The large number of polymorphic variants in the D antigen is accounted for by single or several nucleotide changes or genetic recombinations in RHD,” the authors stated.
The donor’s RhD blood group screening was carried out via use of a saline tube that contained immunoglobulin M (IgM) anti-D. For confirmation of the results, an indirect antiglobulin test was performed with the use of three anti-D clones. The presence or absence of D epitopes was established by testing red blood cells with a D-screen identification kit.
Read more about the symptoms of and risks of HDFN
Serologic testing with different anti-D reagents established the presence of a weakened D phenotype. The blood type of the RhCE phenotype was determined to be C+c+E–e+.
Among the Chinese Han population to which the donor belongs, the weak D phenotype is a rare occurrence, which is reported in 0.01% of individuals. In the present analysis, serologic tests and D sequencing were used to identify the novel RHD allele with the c.336T>G variant.
Although the novel c.336T>G mutation is known to occur at the “first base of exon three near the RHD splice site consensus sequence,” predictions based on several tools utilized for splicing detection imply that the variant actually may not impact splicing. In fact, the splicing interference was not considered to be responsible for the quantitative defect seen in this patient.
The amino acid alteration at residue 112, which likely took place in the transmembrane region that spans the erythrocyte membrane, might be associated with impaired membrane integration and D protein expression. This, in turn, might result in a weak D antigen phenotype.
Of note, the RHD allele with diverse amino residues at p.112 demonstrated variable effects on expression of the D antigen. There have been a number of similar situation reported in which the missense mutation occurs at this position. These findings underscore the fact that the nucleotide change observed at the same amino acid residue may be associated with varying RhD expression.
The novel RHD allele contributes new data to the current “repertoire of knowledge on weak D antigen expression causing RHD alleles,” the authors concluded.
