Somatic revertant mosaicism in a patient with leukocyte adhesion deficiency type 1
Somatic revertant mosaicism in a patient with leukocyte adhesion deficiency type 1
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DOI：
10.1182/blood-2006-08-039057
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发表时间：
2007-02-01
期刊：
影响因子：
20.3
通讯作者：
Yachie, Akihiro
中科院分区：
文献类型：
--
作者：
Tone, Yumi;Wada, Taizo;Yachie, Akihiro
白细胞粘附缺陷 1 型 (LAD-1) 是一种由 ITGB2 (CD18) 基因突变引起的常染色体隐性遗传疾病，其特征是反复严重感染、脓液形成受损和伤口愈合缺陷。我们描述了一个不寻常的严重表型 LAD-1 表现为体细胞嵌合的病例。该患者是一个复合杂合子，带有两种不同的移码突变，这些突变会消除蛋白质表达。然而，CD18 表达在一小部分 T 细胞中检测到，但在粒细胞、单核细胞、B 细胞和自然杀伤 (NK) 细胞中检测不到。 T细胞不是母本来源，缺乏父本突变，并且在体内表现出选择性优势。使用分选的CD18+细胞进行的分子分析表明它们源自携带T细胞受体VB22的单个CD8+T细胞。这些发现表明，自发的体内逆转是导致该患者体细胞嵌合的原因。
Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive disorder caused by mutations in the ITGB2 (CD18) gene and characterized by recurrent severe infections, impaired pus formation, and defective wound healing. We describe an unusual case of severe phenotypic LAD-1 presenting with somatic mosaicism. The patient is a compound heterozygote bearing 2 different frame-shift mutations that abrogate protein expression. However, CD18 expression was detected in a small proportion of T cells but was undetectable in granulocytes, monocytes, B cells, and natural killer (NK) cells. The T cells were not of maternal origin, lacked the paternal mutation, and showed a selective advantage in vivo. Molecular analysis using sorted CD18(+) cells revealed them to be derived from a single CD8(+) T cell carrying T-cell receptor VB22. These findings suggest that spontaneous in vivo reversion was responsible for the somatic mosaicism in our patient.