PIK3CD功能获得性突变致慢性EB病毒感染1例并文献复习  

CHRONIC EPSTEIN-BARR VIRUS INFECTION DUE TO A GAIN-OF-FUNCTION MUTATION OF THE PIK3CD GENE:A CASE REPORT AND LITERATURE REVIEW

作　　者：牛和娣 柏翠[1] 王高燕[3] 王大海 张冉冉 王加兰 常红[1] 邵乐平 林毅[1] NIU Hedi;BAI Cui;WANG Gaoyan;WANG Dahai;ZHANG Ranran;WANG Jialan;CHANG Hong;SHAO Leping;LIN Yi(Pediatric Renal Rheumatology and Immunology Department,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院儿童肾脏风湿免疫科,山东青岛266003 [2]平邑县人民医院 [3]青岛大学附属医院平度院区综合儿科 [4]青岛市市立医院肾内科

出　　处：《精准医学杂志》2023年第1期47-50,共4页Journal of Precision Medicine

基　　金：国家自然科学基金资助项目(81873594)。

摘　　要：目的报道1例PIK3CD基因功能获得性(GOF)突变致慢性EB病毒(EBV)感染患儿,探讨该病临床表现及基因突变特点。方法收集患儿的临床资料,提取患儿及直系亲属外周血DNA,通过全外显子组测序技术检测其基因突变情况,并检索相关文献进行复习。结果患儿自2岁始反复出现呼吸道感染,伴肝脾淋巴结肿大,反复出现种痘样皮疹;血清EBV抗体水平显著升高,淋巴组织活检提示T淋巴细胞增殖性改变,EBV编码RNA(EBER)阳性。13岁时患儿血液中免疫球蛋白水平显著升高伴多种自身抗体阳性。基因检测提示PIK3CD基因杂合突变c.3061G>A(p.E1021K),文献复习提示该突变为GOF突变。结论PIK3CD基因GOF突变可导致EBV易感及EBV慢性感染,临床表现为淋巴组织增生、特征性皮疹出现。该病患儿亦可表现为血液中免疫球蛋白水平的显著升高,可能与自身免疫反应所致自身抗体大量形成有关。Objective To investigate the clinical manifestations and gene mutation characteristics of chronic Epstein-Barr virus(EBV)infection caused by a gain-of-function(GOF)mutation of the PIK3CD gene through a case report.Methods The clinical data of a pediatric patient was collected,and whole-exome sequencing was used to detect gene mutations.Related articles were searched and reviewed.Results The pediatric patient experienced recurrent respiratory infection since 2 years of age accompanied by enlargement of liver,spleen,and lymph nodes and recurrent varicella-like rash.There was a significant increase in the serum level of EBV antibody,and lymphoid tissue biopsy showed T lymphocyte proliferative changes and positive EBV-encoded RNA.At the age of 13 years,the pediatric patient experienced a significant increase in the level of immunoglobulins in blood with various positive autoantibodies.Genetic testing revealed a heterozygous mutation in the PIK3CD gene,c.3061G>A(p.E1021K),and literature review showed that this mutation was a GOF mutation.Conclusion The GOF mutation of the PIK3CD gene can lead to susceptibility to EBV and chronic EBV infection,with the clinical manifestations of lymphoid hyperplasia and characteristic rash.Pediatric patients with this disease can also present with significant increases in the levels of immunoglobulins in blood,which may be associated with the formation of massive autoantibodies caused by autoimmune response.

关 键 词：PIK3CD基因 PI3Kδ过度活化综合征 功能获得性突变 爱泼斯坦巴尔病毒感染 全外显子组测序 体征和症状 突变 

分 类 号：R394.3[医药卫生—医学遗传学] R512.99[医药卫生—基础医学]