Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Department of Pediatrics, Al-Hussein Teaching Hospital, Samawah, Muthanna, Iraq.
BMC Med Genet. 2019 Jun 26;20(1):114. doi: 10.1186/s12881-019-0837-4.
Dedicator of cytokinesis 8 (DOCK8) deficiency (MIM #243700) is a rare disease, leads to a combined primary immunodeficiency (PID), and accounts for the autosomal recessive-hyper immunoglobulin E syndrome (AR-HIES). DOCK8 deficiency status characterizes by recurrent infections, atopy, and risk of cancer. Lymphoproliferative disease complicating PID, is difficult to diagnose. Our aim is to present a rare case of PID, and to the best of our knowledge, she is the first case of DOCK8 deficiency from Iraq. The genetic diagnosis was carried out in Japan using dried blood spot-based DNA transfer and whole-exome sequencing.
An 11-year-old Iraqi girl, of double first-cousin-parents, had a history of severe eczema, food allergy, and repeated infections. She presented with a jaw mass, bilateral cervical and axillary lymphadenopathy, and immunoglobulin (Ig) assays of 20, 3.3 and 1.7-fold above maximum normal level for age of IgE, IgA and IgG, respectively, along with a low IgM, eosinophilia and lymphopenia. Based on the jaw mass biopsy, non-Hodgkin lymphoma was suggested in Iraq, whereas histopathological re-evaluation in Japan revealed the diagnosis of a polyclonal reactive proliferation spectrum of lymphoproliferative disorders/plasmacytic hyperplasia, complicating PID. Whole-exome sequencing supported the diagnosis of PID by identifying a homozygous DOCK8 mutation with previously reported pathogenicity (NM_203447:c.3332delT, p.Phe1113Leufs*2), that may be attributed to consanguinity.
International collaboration using an effective DNA transportation technique and next-generation sequencing was the key to pinpoint the diagnosis of DOCK8 deficiency. Our case asserted that careful pathogenetic evaluation, in an advanced setting, was crucial for ruling out the neoplastic process. Pediatricians in areas with a high prevalence of consanguinity marriage should have a high index of suspicion of DOCK8 deficiency in patients with recalcitrant eczema, and frequent respiratory and skin infectious episodes.
胞分裂蛋白 8（DOCK8）缺乏症（MIM #243700）是一种罕见疾病，导致联合原发性免疫缺陷（PID），并占常染色体隐性高免疫球蛋白 E 综合征（AR-HIES）。DOCK8 缺乏症的特征是反复感染、特应性和癌症风险。PID 并发的淋巴增生性疾病难以诊断。我们旨在介绍一例罕见的 PID 病例，据我们所知，她是来自伊拉克的首例 DOCK8 缺乏症病例。基因诊断在日本通过干血斑 DNA 转移和全外显子组测序进行。
一名 11 岁的伊拉克女孩，有双表亲父母，患有严重湿疹、食物过敏和反复感染。她表现为下颌肿块、双侧颈和腋窝淋巴结肿大，免疫球蛋白（Ig）检测结果分别为 IgE、IgA 和 IgG 年龄最大正常值的 20 倍、3.3 倍和 1.7 倍，同时伴有 IgM 低、嗜酸性粒细胞增多和淋巴细胞减少。根据下颌肿块活检，在伊拉克提示非霍奇金淋巴瘤，而在日本的重新评估表明诊断为多克隆反应性增殖谱的淋巴增生性疾病/浆细胞增生，并发 PID。全外显子组测序通过识别先前报道的致病性同源纯合 DOCK8 突变（NM_203447：c.3332delT，p.Phe1113Leufs*2）支持 PID 的诊断，这可能归因于近亲结婚。
使用有效 DNA 转运技术和下一代测序的国际合作是确定 DOCK8 缺乏症诊断的关键。我们的病例表明，在高级环境中进行仔细的发病机制评估对于排除肿瘤过程至关重要。在近亲结婚高发地区的儿科医生应该对顽固湿疹和频繁呼吸道和皮肤感染发作的患者高度怀疑 DOCK8 缺乏症。
