An initiation codon mutation in CD 18 in association with the moderate phenotype of leukocyte adhesion deficiency

James E Sligh, Mary Y. Hurwitz, Chengming Zhu, Donald C. Anderson, Arthur L. Beaudet

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Leukocyte adhesion deficiency (LAD) is an autosomal recessive disease caused by mutations in the CD 18 gene which codes for the β2 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 (<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).

Original languageEnglish (US)
Pages (from-to)714-718
Number of pages5
JournalJournal of Biological Chemistry
Volume267
Issue number2
StatePublished - Jan 15 1992
Externally publishedYes

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Initiator Codon
Leukocytes
Adhesion
Phenotype
Frameshift Mutation
Mutation
Complementary DNA
Codon
Mothers
Aspartic Acid
Integrins
Protein Biosynthesis
Blood
Genes
Fathers
RNA
Amino Acids
Messenger RNA
Defects
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

An initiation codon mutation in CD 18 in association with the moderate phenotype of leukocyte adhesion deficiency. / Sligh, James E; Hurwitz, Mary Y.; Zhu, Chengming; Anderson, Donald C.; Beaudet, Arthur L.

In: Journal of Biological Chemistry, Vol. 267, No. 2, 15.01.1992, p. 714-718.

Research output: Contribution to journalArticle

Sligh, James E ; Hurwitz, Mary Y. ; Zhu, Chengming ; Anderson, Donald C. ; Beaudet, Arthur L. / An initiation codon mutation in CD 18 in association with the moderate phenotype of leukocyte adhesion deficiency. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 2. pp. 714-718.
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