V(D)J recombination, during which recognition and repair of broken DNA chains are accomplished by non-homologous end joining pathway, is a critical process in B and T cell development.Null mutations of each enzyme or protein of this pathway result in T- B- NK+ severe combined immunodeficiency whereas hypomorphic mutations result in atypical(leaky)severe combined immunodeficiency forms. We present two siblings with PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) mutation who presented with granulomatous skin lesions and recurrent lung infections. Primary immune deficiencies may initially present with skin findings. Disruption in central and peripheral B-cell tolerance and impaired intrathymic T-cell maturation,a central player in T-cell tolerance, have been identified as the mechanism of autoimmunity and granuloma seen in patients. The variation in clinical phenotypes of patients with PRKDC mutation suggests that additional factors such as modifying genes, epigenetic and environmental factors may affect the severity and clinical phenotype of the disease. Functional studies during the follow-up and evaluation before and after hematopoeitic stem cell transplantation will hopefully increase our knowledge about the autoimmune and inflammatory process of the disease spectrum.

V（D）J重组是B和T细胞发育的关键过程，在此过程中，DNA断裂的链的识别和修复是通过非同源末端连接途径完成的，该途径中每种酶或蛋白质的无效突变都会导致T -B- NK +严重的联合免疫缺陷，而亚型突变导致非典型（渗漏）严重的联合免疫缺陷。我们介绍了两个患有PRKDC（蛋白激酶，DNA激活，催化多肽）突变的兄弟姐妹，他们出现肉芽肿性皮肤病变和肺部反复感染。最初的免疫缺陷可能最初出现在皮肤上。中枢和外周B细胞耐受性的破坏以及胸腺内T细胞成熟性的破坏（T细胞耐受性的重要参与者）已被确定为患者体内自身免疫和肉芽肿的机制。PRKDC突变患者临床表型的变化表明，诸如修饰基因，表观遗传和环境因素等其他因素可能会影响疾病的严重程度和临床表型。造血干细胞移植前后的随访和评估过程中的功能性研究有望增加我们对疾病谱的自身免疫和炎症过程的了解。