Familial genetic defect in a case of leukocyte adhesion deficiency

✍ Scribed by Yoshiyuki Ohashi; Takaaki Yambe; Shigeru Tsuchiya; Hideaki Kikuchi; Tasuke Konno

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 919 KB
• Volume: 2
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380020606

✦ Synopsis

Communicated by Charles J. Epstein Leukocyte adhesion deficiency (LAD) is an inherited immunodeficiency disorder caused by CD 18 subunit abnormality dependent defective expression of pz integrins on the surface of leukocytes. On analysis of the CD18 molecular defect in a female Japanese patient with a severe deficiency LAD phenotype, neither CDl l a nor CD18 molecules could be detected on the patient's EBV-transformed B lymphoblastoid cell line. The mRNA of the patient's B cells was normal in size, but was diminished in quantity, to approximately half normal levels. Sequencing of the CD18 cDNA of the patient revealed a C605 to T transition, resulting in a Pr~'~'-+Leu substitution. This was heterozygous in the genomic DNA, and shown to be of maternal origin by family study. Only a few transcripts from the other allele without the Pro' 78-+Leu mutation were detectable. Northern blot analysis revealed reduced CD18 mRNA levels, not only in the patient, but also in the father and brother. These results indicate that our case is a compound heterozygote with two different mutant alleles: one causing a single amino acid substitution and the other causing defective expression of mRNA.