Typical hyper-IgE syndromes (HIES) are caused by autosomal-dominant-negative (DN) variants of STAT3 (Signal Transducer And Activator Of Transcription 3) or IL6ST (Interleukin 6 Cytokine Family Signal Transducer), biallelic partial loss-of-function (LOF) variants of IL6ST, or biallelic complete LOF variants of ZNF341 (Zinc Finger Protein 341). Including the two new cases described in this review, only 20 patients with autosomal-recessive (AR) ZNF341 deficiency have ever been reported. Patients with AR ZNF341 deficiency have clinical and immunological phenotypes resembling those of patients with autosomal-dominant STAT3 deficiency, but with a usually milder clinical presentation and lower NK (Natural Killer) cell counts. ZNF341-deficient cells have 50% the normal level of STAT3 in the resting state. However, as there is no clear evidence that STAT3 haploinsufficiency causes HIES, this decrease alone is probably insufficient to explain the HIES phenotype observed in the ZNF341-deficient patients. The combination of decreased basal expression level and impaired autoinduction of STAT3 observed in ZNF341-deficient lymphocytes is considered a more likely pathophysiological mechanism. We review here what is currently known about the ZNF341 gene and ZNF341 deficiency, and briefly discuss possible roles for this protein in addition to its control of STAT3 activity.

典型的高 IgE 综合征 (HIES) 是由STAT3（信号转导器和转录激活剂 3）或IL6ST（白细胞介素 6 细胞因子家族信号转导器）的常染色体显性阴性 (DN) 变体、双等位基因部分功能丧失 ( IL6ST的 LOF) 变体，或ZNF341（锌指蛋白 341）的双等位基因完整 LOF 变体。包括本综述中描述的两例新病例在内，仅报告了 20 例常染色体隐性 (AR) ZNF341 缺陷患者。AR ZNF341 缺陷患者的临床和免疫表型与常染色体显性 STAT3 缺陷患者相似，但临床表现通常较轻，NK（自然杀伤）细胞计数较低。ZNF341 缺陷细胞在静息状态下的 STAT3 水平只有正常水平的 50%。然而，由于没有明确的证据表明 STAT3 单倍体不足会导致 HIES，因此这种下降可能不足以解释在 ZNF341 缺陷患者中观察到的 HIES 表型。在 ZNF341 缺陷淋巴细胞中观察到的 STAT3 基础表达水平降低和自诱导受损的组合被认为是更可能的病理生理机制。我们在此回顾目前对ZNF341基因和 ZNF341 缺陷的了解，并简要讨论该蛋白除了控制 STAT3 活性之外的可能作用。