Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare inherited disorder leading to severe organ-specific autoimmunity. IPEX is caused by hemizygous mutations in FOXP3, which codes for a master transcription factor of regulatory T (T_Reg) cell development and function.

We describe a four-year-old boy with typical but slightly delayed-onset of IPEX with autoimmune diabetes mellitus, enteropathy, hepatitis and skin disease. We found the unreported FOXP3 splice site mutation c.816+2T>A that leads to the loss of leucine-zipper coding exon 7. RNA-Seq revealed that FOXP3Δ7 leads to differential expression of FOXP3 regulated genes. After myeloablative conditioning the patient underwent allogeneic HSCT from a matched unrelated donor. HSCT led to the resolution of all IPEX symptoms including insulin requirement despite persisting autoantibody levels. After initial full donor engraftment nearly complete autologous reconstitution was documented, but donor-derived T_Reg cells persisted with a lineage-specific chimerism of >70% and the patient remained in clinical remission.

免疫失调，多内分泌病，肠病，X连锁（IPEX）综合征是一种罕见的遗传性疾病，可导致严重的器官特异性自身免疫。IPEX由FOXP3中的半合子突变引起，该突变编码调节性T（T _Reg）细胞发育和功能的主要转录因子。

我们描述了一个四岁男孩，患有典型但稍延迟的IPEX发作，伴有自身免疫性糖尿病，肠病，肝炎和皮肤病。我们发现未报告的FOXP3剪接位点突变c.816 + 2T> A导致亮氨酸拉链编码外显子7的丢失。RNA-Seq显示FOXP3Δ7导致FOXP3调控基因的差异表达。进行清髓治疗后，患者从匹配的无关亲戚那里接受了同种异体造血干细胞移植。尽管自身抗体水平持续存在，HSCT仍可解决所有IPEX症状，包括胰岛素需求。在最初的完全供体植入后，有近乎完全的自体重建记录，但来自供体的T _Reg 细胞持续以> 70％的谱系特异性嵌合体持续存在，患者仍处于临床缓解期。