Single allele mutations in the Cell Division Control protein 42 homolog (CDC42) gene were recently shown to cause Takenouchi-Kosaki syndrome with diverse manifestations. These include persistent mild thrombocytopenia with large platelet size, severe developmental delay, growth retardation, facial dysmorphism, and other neurodevelopmental and hematological anomalies. CDC42 deficiency might also cause myelofibrosis, myeloproliferation, and severe autoinflammation. CDC42 closely interacts with the Wiskott-Aldrich Syndrome Protein, but little is still known about the immune abnormalities associated with CDC42 deficiency. Detailed immune evaluations were performed in a patient diagnosed with a CDC42 Tyr64Cys mutation. The 19-year-old female suffered from recurrent pneumonia, otitis media, and bacteremia, which resolved at 10 years of age, concordant with the initiation of amoxicillin prophylaxis. In addition, the patient had frequent viral upper respiratory tract infections, which resolved without need for medical interventions. Immune evaluations demonstrated decreased immunoglobulin levels, inability to maintain antibody responses, progressive decline in the number of CD19+ B cells, and decreased switched memory B cells. There was also a decrease in CD4+ and CD8+ T cells, markedly reduced naïve T cells, and intermittent depressed proliferation of T cells to stimulation. Natural killer cells’ number and functions were normal. However, no opportunistic infections were observed, nor was there evidence for autoinflammation. CDC42 deficiency might also be associated with decline in T and B cell function. Therefore, immunity in patients with CDC42 defects should be closely monitored, particularly among those with frequent infections or systemic autoinflammation.

最近显示细胞分裂控制蛋白 42 同源 (CDC42) 基因中的单个等位基因突变会导致具有多种表现的竹内小崎综合征。这些包括持续性轻度血小板减少症伴大血小板、严重发育迟缓、生长迟缓、面部畸形以及其他神经发育和血液学异常。CDC42 缺乏也可能导致骨髓纤维化、骨髓增生和严重的自身炎症。CDC42 与 Wiskott-Aldrich 综合征蛋白密切相互作用，但对与 CDC42 缺乏相关的免疫异常知之甚少。在诊断为 CDC42 Tyr64Cys 突变的患者中进行了详细的免疫评估。19岁女性反复肺炎、中耳炎、菌血症，10岁时痊愈，与阿莫西林预防的开始一致。此外，患者经常出现病毒性上呼吸道感染，无需医疗干预即可解决。免疫评估表明免疫球蛋白水平降低、无法维持抗体反应、CD19+ B 细胞数量逐渐减少以及转换记忆 B 细胞减少。CD4+ 和 CD8+ T 细胞也有所减少，幼稚 T 细胞显着减少，T 细胞对刺激的增殖间歇性抑制。自然杀伤细胞的数量和功能正常。然而，没有观察到机会性感染，也没有发现自身炎症的证据。CDC42 缺乏也可能与 T 和 B 细胞功能下降有关。因此，应密切监测CDC42缺陷患者的免疫力，