Partial D variant with demonstrated risk of D alloimmunization in the Australian Indigenous population.

Abstract

Background and objectives: Two prior publications have identified a novel RHD variant in the Australian population with the pattern of single nucleotide variation (SNV) c.186G>T, c.410C>T, c.455A>C, c.602C>G, c.604G>A, c.733G>C, and a deletion or rearrangement with RHCE exon 9. The Australian Red Cross Lifeblood provides testing across Australia, and over a period of 8 years, this same RHD variant has been noted, with some cases presenting with allogeneic anti-D.

Materials and methods: Cases with the combination of SNVs were identified with the RHD BeadChip™ panel and massively parallel sequencing, and were collated. Clinical presentation, phenotype and the specificity of any antibodies were also reviewed.

Results: Twelve cases of the same pattern of SNV and exon change were identified. There was consistent finding of c.186G>T, c.410C>T, c.455A>C, c.602C>G, c.604G>A and c.733G>C, in association with RHCE replacement of exon 9. All cases except one were phenotypically D-positive. Nine of 12 cases presented with anti-D antibodies, often associated with pregnancy. Where ethnicity was reported, all individuals were of Australian Indigenous ethnicity.

Conclusion: This RHD variant is observed to date only in people of Australian Indigenous ethnicity and has clinical relevance. With wider knowledge of the variant, it is anticipated that there will be increased screening in this population, especially in women of childbearing age.