Stable inheritance of an HLA-'blank' phenotype associated with a structural mutation in the HLA-A(*)0301 gene

Abstract

A serological family study identified an HLA-A 'blank' segregating through three generations of apparently healthy individuals. The HLA-A(*)0301 allele was assigned by DNA genotyping in each of the three individuals. Complete absence of cellular expression of the HLA-A3 antigen was associated with a 6 nucleotide deletion in exon 3 of the A(*)0301 gene. The in-frame deletion of nucleotides 373-378 results in the absence of residues C101 and D102 from the mature HLA-A heavy chain. Cysteine 101 is involved in the formation of the highly conserved disulfide bridge in the α2 domain of the class I molecule, and deletion of this residue is believed to be highly disruptive to proper folding and func..