An initiation codon mutation in CD18 in association with the moderate phenotype of leukocyte adhesion deficiency

J Biol Chem. 1992 Jan 15;267(2):714-8.


Leukocyte adhesion deficiency (LAD) is an autosomal recessive disease caused by mutations in the CD18 gene which codes for the beta 2 integrin subunit. We studied two patients, the first of which had a moderate LAD phenotype and expressed only 9% of CD11/CD18 on blood leukocytes. RNA from lymphoblasts was reverse-transcribed, and the cDNA was amplified, cloned, and sequenced. An ATG to AAG alteration in the initiation codon was detected in 39 of 45 (87%) cDNA clones. This mutation was detected in the father, but not in the mother. The maternal defect was shown to be a frameshift mutation with the deletion of a single T in the aspartic acid codon at position 690 (GAT), 11 amino acids N-terminal to the beginning of the transmembrane domain. This mutation predicts a polypeptide which would terminate without transmembrane or cytoplasmic domains. The frameshift mutation was also found in the second patient who had the severe phenotype of LAD (less than 1% of CD11/CD18), indicating that this allele does not encode a functional protein. The partial expression in the patient with a moderate phenotype must be derived from the initiation codon mutation and may be due to a low level of initiation of translation of the CD18 mRNA at the second codon (CUG).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / genetics*
  • Base Sequence
  • CD11 Antigens
  • CD18 Antigens
  • Child
  • Codon
  • DNA / genetics
  • Fluorescent Antibody Technique
  • Frameshift Mutation*
  • Humans
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Phenotype*
  • Polymerase Chain Reaction
  • Receptors, Leukocyte-Adhesion / genetics*
  • Sequence Homology, Nucleic Acid


  • Antigens, CD
  • CD11 Antigens
  • CD18 Antigens
  • Codon
  • Receptors, Leukocyte-Adhesion
  • DNA

Associated data

  • GENBANK/L01675
  • GENBANK/L01676
  • GENBANK/L01677
  • GENBANK/M81836
  • GENBANK/M83679
  • GENBANK/M83680
  • GENBANK/M83681
  • GENBANK/M83724
  • GENBANK/S75297
  • GENBANK/S75381