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• W2753682912 abstract "With an increasing ability to routinely sequence areas of HLA loci outside of those sequenced historically, notably the antigen-binding region, comes the discovery of an increasing number of new alleles due to the ability to discern novel mutations in these newly-sequenced areas. Occasionally, though, the appearance of a novel mutation outside the antigen-binding region can result in an ambiguous type which may lead to a misidentification of the alleles as determined by the sequence of the antigen-binding region alone; this may lead to a clinically significant adverse outcome. During routine HLA typing of a patient in preparation for bone marrow transplant, our lab typed his DPB1 as DPB1∗23:01, DPB1∗81:01, a common/common combination, using sequence-based typing (SBT). The more common combination DPB1∗02:01, DPB1∗04:01 was ruled out by a single nucleotide in exon 3, which is outside of the antigen-binding region. Verification typing of this patient using sequence-specific primers and typing of an HLA-matched sibling resulted in a type of DPB1∗02:01:02G, DPB1∗04:01:01G, however, and ruled out DPB1∗23:01 and DPB1∗81:01 as potential alleles. Further investigation of the SBT result revealed that running a group-specific sequencing primer that targets exon 2 (the antigen-binding region for DPB1) also rules out DPB1∗23:01 and DPB1∗81:01 as potential alleles. Therefore, the verification typing of DPB1∗02:01:02G, DPB1∗04:01:01G was correct, since this typing refers only to the clinically significant antigen-binding region. The nucleotide in exon 3 that led to the initial rule-out of this type was likely a novel mutation, and the result of DPB1∗23:01, DPB1∗81:01 remained only because the exon 3 sequence for DPB1∗81:01 is not currently in the IMGT HLA database. Had this result remained in the patient’s record, it may have led to a clinically significant mismatch with the eventual donor (although both combinations are contained in the same T-cell epitope group)." @default.
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• W2753682912 date "2017-09-01" @default.
• W2753682912 modified "2023-09-26" @default.
• W2753682912 title "P091 Novel mutation in a non-key exon of DPB1 leads to miscall of alleles as determined by antigen-binding-region sequence" @default.
• W2753682912 doi "https://doi.org/10.1016/j.humimm.2017.06.151" @default.
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