Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children\'s Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Pediatric department of Bou-Ali educational Hospital, Ardabil university of medical sciences, Ardabil, Iran.
Endocr Metab Immune Disord Drug Targets. 2022;22(1):159-168. doi: 10.2174/1871530321666210226143912.
Dedicator of Cytokinesis 8 (DOCK8) deficiency, the most frequent cause of autosomal recessive hyper immunoglobulin (Ig)E syndrome, is a rare combined immunodeficiency.
In this study, we report seven patients, with consanguineous parents, with five novel variants within the DOCK8 gene.
For genetic analysis, we performed Whole Exome Sequencing (WES) or targeted sequencing by means of Next-generation sequencing (NGS) for some of the patients. For others, Sanger sequencing, Fluorescence-activated cell sorting (FACS), or polymerase chain reaction (PCR) were used.
We report five novel variants within the DOCK8 gene: three deletions (deletion of exons 4-12, 24-30, and 22-27), one frameshift (LRG_196:g.189315dup;p.(Leu1052Profs*7)), and a splice region variant (LRG_196t1:c.741+5G>T). Patients presented with skin lesions, food allergy, candidiasis, otitis, recurrent respiratory infections, short stature, aortic aneurism, gynecomastia, and coarse facial features. Patients had leukocytosis, eosinophilia, lymphopenia, and monocytosis, elevated IgE, IgG, IgA, reduced IgM and IgA levels. Patients had a low percentage of CD3+ and CD4+ cells and a high percentage of CD19+, CD27+CD19+, and recent thymic emigrants T cells. The percentage of natural killer cells was increased in one of the patients while it was decreased in another patient. One patient died due to disseminated intravascular coagulation after hematopoietic stem cell transplantation.
We reported novel variants within the DOCK8 gene and highlighted the risk of aneurysms in these patients, which have been rarely reported in these patients.
细胞分裂启动因子 8（DOCK8）缺陷是常染色体隐性遗传高免疫球蛋白 E 综合征的最常见原因，是一种罕见的联合免疫缺陷。
在这项研究中，我们报告了 7 名患者，他们的父母为近亲，DOCK8 基因中存在 5 个新的变异体。
对于遗传分析，我们对一些患者进行了全外显子组测序（WES）或下一代测序（NGS）的靶向测序。对于其他患者，则使用 Sanger 测序、荧光激活细胞分选（FACS）或聚合酶链反应（PCR）。
我们报告了 DOCK8 基因中的 5 个新变异体：3 个缺失（外显子 4-12、24-30 和 22-27 的缺失）、1 个移码突变（LRG_196：g.189315dup;p.（Leu1052Profs*7））和 1 个剪接区变异体（LRG_196t1：c.741+5G>T）。患者表现为皮肤损伤、食物过敏、念珠菌病、中耳炎、反复呼吸道感染、身材矮小、主动脉瘤、男性乳房发育和粗糙的面部特征。患者白细胞增多、嗜酸性粒细胞增多、淋巴细胞减少和单核细胞增多、IgE、IgG、IgA 升高、IgM 和 IgA 水平降低。患者 CD3+和 CD4+细胞比例低，CD19+、CD27+CD19+和近期胸腺迁出 T 细胞比例高。一名患者的自然杀伤细胞百分比增加，另一名患者的自然杀伤细胞百分比减少。一名患者在造血干细胞移植后死于弥散性血管内凝血。
我们报告了 DOCK8 基因中的新变异体，并强调了这些患者发生动脉瘤的风险，这些患者很少有报道。
