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

MUFARREGE, NICOLÁS; TRUCCO BOGGIONE, CAROLINA; PUPPO, MÓNICA; ENSINCK, ALEJANDRA; PRÍNCIPI, CINTIA; BRAJOVICH, MELINA LUJÁN; MATTALONI, STELLA; BIONDI, CLAUDIA; KUPERMAN, SILVINA; COTORRUELO, CARLOS

TRANSFUSION

WILEY-BLACKWELL PUBLISHING, INC

Año: 2020 vol. 60

0041-1132

One novelRHDallele was detected in the analysed popula-tion of Argentina. The missense mutation c.325A>G isresponsible for the amino acidic change p.Thr109Ala,predicted to be in the extracellular boundary of the fourthtransmembrane segment of the RhD protein. This newallele has been submitted to GenBank with accession num-ber MN262645 and was designated by the ISBT asRHD*66.The polymorphism had been annotated as rs1376983227 inthe GnomAD database and is present in only one Africanindividual with an allele frequency of 0.00006424. Interest-ingly, the three samples harboring the aforementionedmutation showed the agglutination pattern of a DFR phe-notype as indicated by the ID-Partial RhD typing set(Table 1). While the already-reported five DFR variantsresult from hybrid structures involvingRHDExon 4 (andalso Exon 3 in DFR-5),1,2apointmutationinRHDExon2 is responsible for the new allele described in this work.Serologic and molecular results suggest a genetic associa-tion incisbetween this newRHDvariant and theRHCE*Ceallele (Table 1). Surprisingly, the novelRHD*66allele wasfound in 2.48% (3/121) of serologic weak D samples fromthe central area of Argentina. We can speculate that theRHD*66allele could not be attributed to the Amerindiangenetic influence as no sample from the Northwesternarea-where the native contribution is higher than in otherparts of the country-exhibited the c.325A>G SNV. Thisnew variant could be related rather to the Caucasiangenetic component that predominates in the centralregion.5Our findings suggest that aRHDgenotyping strat-egy for our population should consider the detection of thisrelatively prevalentRHD*66allele