Genotyping confirms inheritance of the rare At(a−) type in a case of haemolytic disease of the newborn

Abstract

The Ata blood group antigen (now AUG2 in the Augustine system) is a high‐frequency antigen with negative phenotype At(a−) found only in individuals of African ancestry. In a twin pregnancy, the fifth pregnancy in a woman of African origin, serological investigations confirmed that the mother was At(a−) and anti‐Ata was detected. DNA samples were exome sequenced and alignment was performed to allow variant calling. It was confirmed that the single nucleotide polymorphism, rs45458701, within the SLC29A1 gene encoding the ENT1 protein, recently reported to be a basis of the At(a−) phenotype was also the basis of the phenotype in this family. The reagents for serological analysis required to identify the rare blood type present in this mother are held in only a few reference laboratories worldwide. This case highlights the utility of genetic methods in resolving complex investigations involving blood grouping and demonstrates that genotyping of variants associated with blood types present in specific ethnic groups may be the fastest method available for identification of the basis of fetomaternal incompatibilities.

Evaluation of targeted exome sequencing for 28 protein‐based blood group systems, including the homologous gene systems, for blood group genotyping

“…These systems incorporate SNVs for the most clinically significant antigens and permit automated blood group phenotype predictions based on genotype . However single nucleotide polymorphism (SNP) typing platforms are limited in both the number of blood group systems covered and the range of SNVs targeted within any blood group . The homologous genes, such as RHD and RHCE in the RH system and GYPA and GYPB in the MNS system, pose particular challenges, because a range of rearranged alleles representing RHD/RHCE and GYPB/GYPA hybrids has resulted from gene‐rearrangement events.…”

A proposed new low‐frequency antigen in the Augustine blood group system associated with a severe case of hemolytic disease of the fetus and newborn

“…Previously, in a mother with an At(a-) phenotype arising from homozygosity of the c.1171G > A variant, a mild case of HDFN due to anti-At a was reported in a fifth pregnancy. 5 Further evidence for the clinical significance of antibodies to antigens in the AUG system is demonstrated in this case study involving an infant affected by severe HDFN.…”

Developments beyond blood group serology in the genomics era

“…In both cases the red cell antigen specificity could not be defined by conventional serology. The genomic outcomes resulted in attributing the antibodies in the first case to the known At(a+) (AUG1) antigen on the maternal red cells; in the second case to a novel antigen, now recognised as AUG3 (McBean et al , ; Millard et al , ). The cases exemplified the clinical significance of antigens in this newly classified blood group.…”