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Familial genetic defect in a case of leukocyte adhesion deficiency
Author(s) -
Ohashi Yoshiyuki,
Yambe Takaaki,
Tsuchiya Shigeru,
Kikuchi Hideaki,
Konno Tasuke
Publication year - 1993
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380020606
Subject(s) - biology , leukocyte adhesion deficiency , compound heterozygosity , microbiology and biotechnology , cd18 , mutation , mutant , heterozygote advantage , frameshift mutation , allele , complementary dna , genetics , phenotype , lymphoblast , gene , integrin , cell culture , cell
Leukocyte adhesion deficiency (LAD) is an inherited immunodeficiency disorder caused by CD18 subunit abnormality dependent defective expression of β 2 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 CD11a 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 C 605 to T transition, resulting in a Pro 178 → 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 178 → 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. © 1993 Wiley‐Liss, Inc.