Broides Arnon, Mandola Amarilla B, Levy Jacov, Yerushalmi Baruch, Pinsk Vered, Eldan Michal, Shubinsky George, Hadad Nurit, Levy Rachel, Nahum Amit, Ben-Harosh Miriam, Lev Atar, Simon Amos, Somech Raz
Pediatric Immunology Clinic, Soroka University Medical Center, Faculty of Health Science, Ben-Gurion University of the Negev. POB151, Beer Sheva, 84101, Israel.
Soroka University Medical Center, Beer Sheva, Israel.
Immunol Res. 2017 Jun;65(3):651-657. doi: 10.1007/s12026-016-8883-x.
Mutations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency usually diagnosed as autosomal recessive hyper IgE syndrome. We sought to reveal the varying manifestations in patients with a unique mutation in DOCK8 gene by a retrospective medical record review. Ten patients from five consanguineous families and three tribes were included. Seven patients were homozygous for the c.C5134A, p.S1711X mutation, and the remaining three patients were their siblings manifesting hyper IgE syndrome features without a genetic diagnosis. Prior to the genetic diagnosis, the clinical diagnosis was "hyper IgE syndrome" in six patients and "anti-pneumococcal antibody deficiency," "recurrent pneumonia with bronchiectasis," and "asthma with hypereosinophilic syndrome" each diagnosed once. One additional patient was diagnosed due to family history. The age of presentation varied from 1 to 16 months. Eczema was diagnosed in all patients, food allergies in three, and severe herpes keratitis or malignancy or autoimmunity in two patients. Elevated IgE was recorded in nine patients; however, in six patients, the initial serum IgE concentration was equal to or less than three times the normal concentration for age, and in these patients, the median age at IgE evaluation was 7.5 months compared with 21.5 months in patients with an initial IgE concentration above three times the normal concentration for age (P = 0.067). The spectrum of disease manifestations in patients with a unique mutation in DOCK8 is variable. The genotype-phenotype correlations may be modified by genetic and/or epigenetic modifiers beyond the monogenic effect. Younger patients tend to have lower IgE concentrations at the initial measurement of IgE.
胞质分裂调控蛋白8（DOCK8）基因突变可导致一种通常被诊断为常染色体隐性高IgE综合征的联合免疫缺陷病。我们通过回顾性病历审查，试图揭示DOCK8基因独特突变患者的不同临床表现。研究纳入了来自5个近亲家庭和3个部落的10名患者。7名患者为c.C5134A、p.S1711X突变的纯合子，其余3名患者为其同胞，表现出高IgE综合征特征但未进行基因诊断。在基因诊断之前，6名患者的临床诊断为“高IgE综合征”，“抗肺炎球菌抗体缺乏症”“支气管扩张伴反复肺炎”和“嗜酸性粒细胞增多综合征伴哮喘”各诊断1例。另有1名患者因家族史确诊。发病年龄从1个月至16个月不等。所有患者均诊断为湿疹，3例有食物过敏，2例有严重疱疹性角膜炎、恶性肿瘤或自身免疫性疾病。9例患者IgE升高；然而，6例患者初始血清IgE浓度等于或低于年龄正常浓度的3倍，这些患者IgE评估的中位年龄为7.5个月，而初始IgE浓度高于年龄正常浓度3倍的患者为21.5个月（P = 0.067）。DOCK8基因独特突变患者的疾病表现谱存在差异。除单基因效应外，基因和/或表观遗传修饰因子可能会改变基因型与表型的相关性。年龄较小的患者在初次检测IgE时往往IgE浓度较低。
