An HLA-B null allele (B*1526N) with a stop codon in exon 3 generated by a point mutation

An HLA-B null allele was identified in a Japanese family during histocompatibility testing for bone marrow transplantation. The propositus was a healthy Japanese woman with three children, and her parents were cousins. Serological HLA typing of the family members indicated that the propositus was homozygous for the A24-Cw4-B blank (B null)-DR4.2-DQ3 haplotype. Total RNA was extracted from peripheral blood of the propositus was converted to first-strand cDNA using reverse transcriptase. The cDNA was amplified by the polymerase chain reaction (PCR) using HLA-B locus-specific primers. The PCR product showed no change in size upon polyacrylamide gel electrophoresis (PAGE) compared to that of normal controls, suggesting that HLA-B gene mRNA was normally expressed. The nucleotide sequence of the cDNA was the same as that of B*1501 except at nucleotide 369 or codon 123, where C was replaced with A; TAC encodes Tyr whereas TAA is a stop codon. This point mutation may have truncated the HLA-B molecule of the propositus, resulting in the negative results we obtained with anti-HLA-B sera.