AN INTRONIC MUTATION RESPONSIBLE FOR A LOW-LEVEL OF EXPRESSION OF AN HLA-A-ASTERISK-24 ALLELE

HLA class I typing performed in parallel by molecular biology and sero logy has revealed cases where an HLA class I allele was identified but the corresponding antigen on the cell surface was not detected. In th e present report, we describe three members of a family in whom an HLA -A24 allele identified at the molecular level was typed as A ''blank'' by lymphocytotoxicity. This serologically blank antigen was neverthel ess faintly detectable by isoelectric focusing (IEF) and FACS analyses , Sequencing of the HLA-A24 allele from the promoter region to the ei ghth exonic region revealed a point mutation in the acceptor site of t he second intron as compared to the normal HLA-A24 allele. This mutat ion could lead to incorrect processing of mRNA through a cryptic accep tor site located at the beginning of the third exon and hence to alter native splicing with a frame shift introducing an early stop codon int o the fourth exon.