Identification of a Rare Haplotype Exhibiting Hemizygosity with Complete Absence of one HLA-B Allele

Body: We report here the case of a 6-year-old female referred to the transplant team for consideration of an allogeneic hematopoietic stem cell transplant (HSCT) as a treatment for severe aplastic anemia (SAA). We performed HLA typing of the patient and her related donors (mother, father and two siblings). Our results showed a case of potential hemizygosity at the HLA-B locus in the patient, the mother and sibling-2, detected with next-generation sequencing using AlloSeq™ Tx 17 based assay with Assign analysis software, and confirmed by copy number variation (CNV) analysis using TypeStream Visual (Fig.1a & b). To confirm hemizygosity and to establish family haplotypes, the patient, mother, father and two siblings' high resolution HLA typing was tested with a secondary method using AllType NGS. We reported to the treating physician the presence of a deletion of one HLA-B allele on the maternal haplotype (c) which was transmitted to children (patient & sibling-2): A*02:01--X--C*07:02-DRB1*04:01-DRB4*01:03-DQB1*03:02-DPB1*105:01 (Table 1).

Conclusion:

Conclusion: The findings highlight the utility of high-throughput sequencing and the dynamic nature of MHC structure and variation which may have implications for immune response, disease susceptibility, and transplantation compatibility. Further investigation using complementary genomic techniques may be necessary to fully characterize the underlying mechanisms responsible for the missing HLA-B allele.