The absence of DR51 in a DRB5-positive individual DR2ES is caused by a null allele (DRB5*0108N)

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Abstract
DR51, a protein encoded by the DRB5 gene, was shown to be present in almost all DR2-positive haplotypes. Exceptions were reported, some DR2-negative samples were shown to be DR51 positive and in a number of DR2-positive samples no DR51 antigen could be demonstrated. In some of them lack of the DRB5 gene was the cause of the absence of DR51 but in others the DRB5 gene was present without resulting in a detectable gene product. Many of these variants were studied in detail in previous international workshops. One of them was DR2ES from our laboratory. She is a DR15-positive DR51-negative individual of oriental origin with a clearly demonstrable DRB5*01 allele when typed by molecular techniques. To unravel the molecular mechanism responsible for the defect in expression, cDNA and DNA encoding the defective DRB5 allele were analyzed. Nucleotide sequence analysis of exon 2 showed no differences from the sequence of DRB5*0102. However, when exon 3 was examined a difference in length was noticed due to a deletion of 19 nucleotides between codon 161 and 168. The deletion caused a frameshift and a premature stopcodon resulting in a null allele. The same allele could be demonstrated in 6 other unrelated individuals of oriental origin as well as in 5 individuals from South Africa. The absence of the DR51 protein was explained by the presence of an alteration in the DRB5 allele resulting in a null allele. The allele has been officially named DRB5*0108N. This is the first description of a null allele of the DRB5 gene.