The novel RHD c.325A>G single nucleotide variation found in Argentineans leads to a partial D phenotype

Abstract

One novel RHD allele was detected in the analysed population of Argentina. The missense mutation c.325A>G is responsible for the amino acidic change p.Thr109Ala, predicted to be in the extracellular boundary of the fourth transmembrane segment of the RhD protein. This new allele has been submitted to GenBank with accession number MN262645 and was designated by the ISBT as RHD*66. The polymorphism had been annotated as rs1376983227 in the GnomAD database and is present in only one African individual with an allele frequency of 0.00006424. Interestingly, the three samples harboring the aforementioned mutation showed the agglutination pattern of a DFR phenotype as indicated by the ID-Partial RhD typing set (Table 1). While the already-reported five DFR variants result from hybrid structures involving RHD Exon 4 (and also Exon 3 in DFR-5),1,2 a point mutation in RHD Exon 2 is responsible for the new allele described in this work. Serologic and molecular results suggest a genetic association in cis between this new RHD variant and the RHCE*Ce allele (Table 1). Surprisingly, the novel RHD*66 allele was found in 2.48% (3/121) of serologic weak D samples from the central area of Argentina. We can speculate that the RHD*66 allele could not be attributed to the Amerindian genetic influence as no sample from the Northwestern area-where the native contribution is higher than in other parts of the country-exhibited the c.325A>G SNV. This new variant could be related rather to the Caucasian genetic component that predominates in the central region.5 Our findings suggest that a RHD genotyping strategy for our population should consider the detection of this relatively prevalent RHD*66 allele.