Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by recurrent bacterial infections, hypogammaglobulinemia and low to normal numbers of circulating B cells. Mutations in the ICOS, TACI and CD19 genes have recently been identified in <10% of CVID patients. We, herein, describe two novel CD19 gene disruptions in an 8-year-old Japanese boy, who had been clinically diagnosed as having CVID at the age of 5 years. Flow-cytometric analysis demonstrated absence of CD19 and reduced CD21 expression on CD20-postive peripheral blood B cells. Mutation analysis of CD19 revealed a mutation in the splice acceptor site of intron 5 (IVS5-1G>T) of the maternal allele, resulting in skipping of exon 6, and a truncated protein product. The paternal allele was disrupted by a gross deletion encompassing at least the ATP2A1, CD19 and NFATC2IP genes. The patient had a small number of IgD(-) CD27(+) memory B cells, in which somatic mutation were detected. His B cells showed substantial proliferation upon stimulation, but reduced IgG and IgA production in vitro. These findings extend the mutation spectrum of the CD19 deficiency to four, and confirm the homogeneity of the CD19 deficiency as a unique type of CVID.

中文翻译：

---

日本CD19缺乏症患者的新型突变。

普通可变免疫缺陷症（CVID）是一种异质性疾病，其特征是细菌反复感染，低球蛋白球蛋白血症和循环B细胞数量低至正常。最近在<10％的CVID患者中发现了ICOS，TACI和CD19基因的突变。我们在本文中描述了一个8岁的日本男孩中的两个新型CD19基因破坏，该男孩在临床上被诊断为5岁时患有CVID。流式细胞仪分析表明，CD20阳性外周血B细胞中不存在CD19，CD21表达降低。CD19的突变分析显示，母亲等位基因内含子5（IVS5-1G> T）的剪接受体位点发生突变，导致外显子6被跳过，蛋白质产物被截短。父本等位基因被至少包含ATP2A1的总体缺失所破坏，CD19和NFATC2IP基因。该患者具有少量的IgD（-）CD27（+）记忆B细胞，其中检测到了体细胞突变。他的B细胞在刺激后显示出实质性增殖，但在体外降低了IgG和IgA的产生。这些发现将CD19缺乏症的突变谱扩展到四个，并确认CD19缺乏症的同质性是CVID的独特类型。