Kumar Jindal Ankur, Sil Archan, Aggarwal Ridhima, Tyagi Rahul, Mondal Sanjib, Singh Ankita, Barman Prabal, Chawla Sanchi, Loganathan Sathish Kumar, Gupta Kirti, Vinay Keshavamurthy, Mahajan Rahul, Saikia Biman, Kaur Gurjeet, Sharma Rajni, Saka Ruchi, Bhatia Anmol, Sankhyan Naveen, Pandiarajan Vignesh, Pilania Rakesh, Dhaliwal Manpreet, Sharma Saniya, Vyas Sameer, Suri Deepti, Rawat Amit, Singh Surjit
Allergy Immunology Unit.
Department of Histopathology.
Clin Exp Dermatol. 2024 Feb 14;49(3):226-234. doi: 10.1093/ced/llad345.
Dedicator of cytokinesis protein 8 (DOCK8) deficiency is an autosomal recessive form of combined immunodeficiency. This rare disorder is characterized by an increased predisposition to allergy, autoimmunity and malignancies.
To analyse clinical, immunological and molecular profiles of patients with DOCK8 deficiency.
Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency.
Median age at diagnosis was 7.5 years (range 2-13), with a male/female ratio of 5 : 1. Among the six patients, recurrent eczematous skin lesions were the predominant cutaneous manifestation, present in five patients (83%). Warts and molluscum contagiosum were evident in two patients (33%) and one patient (16%), respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis-like lesions. Food allergies and asthma were reported by one patient each. Of the six patients, recurrent sinopulmonary infections were detected in five (83%). Epstein-Barr virus-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy, in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in three patients (50%) and five patients (83.3%), respectively. Genetic analysis showed DOCK8 pathogenic variants in all patients: homozygous deletion mutations in two patients, compound heterozygous deletion mutations in one, and homozygous nonsense mutations in two. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient.
DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.
胞质分裂蛋白8（DOCK8）缺陷是一种常染色体隐性联合免疫缺陷病。这种罕见疾病的特征是易患过敏、自身免疫性疾病和恶性肿瘤。
分析DOCK8缺陷患者的临床、免疫学和分子特征。
回顾了2018年至2021年在原发性免疫缺陷门诊就诊的所有患者的临床记录。发现来自五个家庭的六名患者存在DOCK8缺陷。
诊断时的中位年龄为7.5岁（范围2至13岁），男女比例为5:1。在这六名患者中，复发性湿疹样皮肤病变是主要的皮肤表现，五名患者（83%）出现该症状。两名患者（33%）出现疣，一名患者（16%）出现传染性软疣。两名患者有顽固性结节性痒疹病变，两名患者有疣状表皮发育不良样病变。各有一名患者报告有食物过敏和哮喘。六名患者中，五名（83%）检测到复发性鼻窦肺部感染。一名4岁男孩是唯一一例发生肝转移的爱泼斯坦-巴尔病毒驱动的非霍奇金淋巴瘤。所有患者的IgE均升高。分别在三名患者（50%）和五名患者（83.3%）中观察到淋巴细胞减少和嗜酸性粒细胞增多。基因分析显示所有患者均存在DOCK8致病变异：两名患者为纯合缺失突变，一名患者为复合杂合缺失突变，两名患者为纯合无义突变。在一名患者中鉴定出DOCK8基因中的一种新的致病纯合错义变异。
对于任何患有早发性湿疹、皮肤病毒感染且易患过敏、自身免疫性疾病和恶性肿瘤的患者，都应考虑DOCK8缺陷的可能性。
