An intronic mutation responsible for a low level of expression of an HLA-A*24 allele

Tissue Antigens. 1997 Oct;50(4):340-6. doi: 10.1111/j.1399-0039.1997.tb02884.x.

Abstract

HLA class I typing performed in parallel by molecular biology and serology has revealed cases where an HLA class I allele was identified but the corresponding antigen on the cell surface was not detected. In the 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 nevertheless faintly detectable by isoelectric focusing (IEF) and FACS analyses. Sequencing of the HLA-A*24 allele from the promoter region to the eighth exonic region revealed a point mutation in the acceptor site of the second intron as compared to the normal HLA-A*24 allele. This mutation could lead to incorrect processing of mRNA through a cryptic acceptor site located at the beginning of the third exon and hence to alternative splicing with a frame shift introducing an early stop codon into the fourth exon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • DNA Mutational Analysis
  • Female
  • Frameshift Mutation
  • Gene Expression
  • Genes, MHC Class I*
  • HLA-A Antigens / biosynthesis
  • HLA-A Antigens / genetics*
  • HLA-A24 Antigen
  • Humans
  • Introns / genetics*
  • Male
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA Splicing
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Serologic Tests

Substances

  • HLA-A Antigens
  • HLA-A24 Antigen

Associated data

  • GENBANK/Z72422
  • GENBANK/Z72423