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 function of the class I molecule.