Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Chin Med J (Engl). 2010 May 20;123(10):1278-82.
Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, autosomal recessive inherited immunodeficiency disease characterized by recurrent severe bacterial infection, impaired pus formation, poor wound healing, associated with the mutation in the CD18 gene responsible for the ability of the leucocytes to migrate from the blood stream towards the site of inflammation. Correct and early diagnosis of LAD-1 is vital to the success of treatment and prevention of aggressive infections. The purpose of this study was to collect the clinical findings of the disease and to identify the genetic entity.
CD18 expression in the peripheral blood leukocytes from the patient, his parents and normal control was measured with flow cytometry. The entire coding regions of the CD18 gene were screened with direct sequencing genomic DNA.
CD18 expression level on this patient's leukocyte surface was significantly decreased, with normal level in control group, his father and mother. Gene analysis revealed that this patient had a homozygous c.899A > T missense mutation in exon 8 of CD18 gene, causing the substitution of Asp to Val at the 300 amino acid. His parents were both heterozygous carriers while no such mutation was found in 50 normal controls.
This study disclosed a novel point mutation Asp 300 Val located in a highly conserved region (HCR) of CD18 and confirmed the heterogeneity of the mutations causing LAD-1, indicating it was quite beneficial to establish correct and early diagnosis in children with severe LAD-1.
白细胞黏附缺陷 1 型（LAD-1）是一种罕见的常染色体隐性遗传性免疫缺陷病，其特征为反复发生严重的细菌感染、化脓能力受损、伤口愈合不良，与负责白细胞从血流迁移到炎症部位的能力的 CD18 基因突变有关。正确和早期诊断 LAD-1 对治疗和预防侵袭性感染的成功至关重要。本研究旨在收集该疾病的临床发现并确定遗传实体。
采用流式细胞术检测患者、其父母和正常对照者外周血白细胞 CD18 的表达。直接测序基因组 DNA 筛查 CD18 基因的整个编码区。
该患者白细胞表面 CD18 表达水平显著降低，而对照组、其父亲和母亲的水平正常。基因分析显示，该患者在 CD18 基因的第 8 外显子中存在 c.899A > T 错义突变，导致 300 位氨基酸处的天冬氨酸被缬氨酸取代。其父母均为杂合子携带者，而 50 名正常对照者中均未发现该突变。
本研究揭示了一种位于 CD18 高度保守区（HCR）的新型点突变 Asp 300 Val，并证实了导致 LAD-1 的突变存在异质性，这表明对严重 LAD-1 患儿进行正确和早期诊断非常有益。
