Wright A H, Douglass W A, Taylor G M, Lau Y L, Higgins D, Davies K A, Law S K
Department of Biochemistry, University of Oxford, GB.
Eur J Immunol. 1995 Mar;25(3):717-22. doi: 10.1002/eji.1830250313.
Leukocyte adhesion deficiency (LAD) is caused by defects in the CD18 gene, which codes for the common beta 2 subunit of the leukocyte integrins LFA-1, Mac-1 and p150,95. Failure to produce a functional beta 2 subunit results in the defective expression of all three leukocyte integrins, and the leukocytes of LAD patients have subnormal adhesion properties. Six patients with LAD were studied. Patient B was homozygous and carried a G284S mutation. A two-bp (GA) deletion at position 1256 (1256 delta GA) was found in the cDNA of patient C, who also had an abnormally large mRNA of 4.3 kb. Patients E and K were siblings and were heterozygous at the genomic level. One defective allele contained a mutation in intron 6/7 which created a preemptive 3' splice site. The resulting mRNA has 12 extra bases at the junction of exons 6 and 7, coding for four extra residues PSSQ in the protein. The same allele also carried a R586W mutation. The other allele was transcribed at a low level and was not characterized. Patient G carried a L149P mutation in one allele; again, the other allele was not characterized due to low transcription levels. Patient R carried two mutant alleles with G284S and R593C mutations respectively. The G284S mutation and the 1256 delta GA deletion have not been reported previously. CD18 cDNA carrying the abnormalities were cotransfected with normal CD11a or CD11b cDNA into COS cells. Expression of the LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) antigens on COS cells was not detected, suggesting that these two mutations are sufficient to account for LAD.
白细胞黏附缺陷症（LAD）由CD18基因缺陷引起，该基因编码白细胞整合素LFA-1、Mac-1和p150,95的共同β2亚基。无法产生功能性β2亚基会导致所有三种白细胞整合素表达缺陷，LAD患者的白细胞具有黏附特性异常的情况。对6例LAD患者进行了研究。患者B为纯合子，携带G284S突变。在患者C的cDNA中发现第1256位有两个碱基（GA）缺失（1256 delta GA），其mRNA也异常大，为4.3 kb。患者E和K是兄弟姐妹，在基因组水平上为杂合子。一个缺陷等位基因在6号和7号内含子中有一个突变，产生了一个优先的3'剪接位点。所产生的mRNA在6号和7号外显子的连接处有12个额外碱基，在蛋白质中编码四个额外的氨基酸残基PSSQ。同一个等位基因还携带R586W突变。另一个等位基因转录水平低，未进行特征分析。患者G的一个等位基因携带L149P突变；同样，另一个等位基因由于转录水平低未进行特征分析。患者R携带两个分别有G284S和R593C突变的突变等位基因。G284S突变和1256 delta GA缺失以前尚未见报道。将携带异常的CD18 cDNA与正常的CD11a或CD11b cDNA共转染到COS细胞中。未检测到COS细胞上LFA-1（CD11a/CD18）和Mac-1（CD11b/CD18）抗原的表达，表明这两个突变足以解释LAD。
