高IgE综合征及SCN临床与分子特点分析

发布时间：2018-04-21 03:32

本文选题：高lgE综合征 + DOCK8基因　；参考：《重庆医科大学》2012年硕士论文

【摘要】：第一部分：高lgE综合征临床及其分子特点分析目的：探讨7例DOCK8基因突变致高lgE综合征患儿的临床及分子特点。方法：总结7例拟诊为DOCK8基因突变致高lgE综合征的患儿临床资料，包括血常规、免疫球蛋白水平、淋巴细胞分类、病原学检查、影像学检查等。PCR扩增患儿DOCK8cDNA序列并双向测序，发现突变位点后行相应DNA外显子及拼接位点测序分析确定突变类型，并行亲属相关序列测定。结果：DOCK8基因突变致高lgE综合征是常染色体隐性遗传，以生后特应性皮炎、湿疹、反复病毒性皮肤感染，呼吸道感染包括中耳炎、乳突炎、鼻窦炎、肺炎和支气管炎，血清lgE水平明显升高及嗜酸粒细胞血症为主要表现。此7例患儿临床表型均符合DOCK8突变致高lgE综合征临床表现。其中确诊新发突变3例，除外1例，待诊3例。结论：符合DOCK8基因突变致高lgE综合征临床表现的患儿应行该病基因筛查及蛋白检测，这是明确诊断的重要手段。抗病毒药物的使用可以改善临床症状，但是大部分病例因重症感染或皮肤癌而死亡。DOCK8缺陷的重症感染病例，应该强烈考虑造血干细胞移植，但是在感染不太重的病人是否需要造血干细胞还不明确。第二部分：SCN临床及其分子特点分析目的：探讨一例ELANE基因突变致重症先天性中性粒细胞减少症患儿及其临床特征和基因突变。方法：患儿男，1岁6月，，生后表现为脐带脱落延迟（1月余），既往多次重症细菌感染及真菌感染（卡他莫拉菌及大肠埃希菌、铜绿假单胞菌、白色念珠菌），表现为脐炎、反复呼吸道、消化道感染、皮肤感染、颈部淋巴结炎伴脓肿形成、肛周脓肿、肝脏脓肿、真菌性食道炎，行2次脓肿切开引流术及1次肝脓肿切开引流术，后因败血症死亡。多次查外周血中性粒细胞绝对值低于0.5×10^9/L，骨髓检查提示粒系增生偏低，中性粒细胞成熟障碍。父系及母系家族中均无类似患者及夭折史。根据临床表现、免疫学特征拟诊为ELA2基因突变致SCN。提取患儿及父母、哥哥外周血RNA、DNA，采用PCR法扩增ELA2基因，PCR基因产物纯化后进行双向序列测定。结果：对患儿行ELA2基因测序发现，其第4外显子发生插入突变，导致插入5个氨基酸（g.795598_795599insGGACCAGCTGCCGGC;c.439_440insGGACCAGCTGCCGGC; p.134_135insAspGlnLeuProAla）。患儿母亲、父亲、哥哥在该位点为野生型。结论：通过临床特征及基因测序，确诊1例ELA2基因突变致SCN患儿。SCN为常染色体显性遗传的骨髓衰竭综合征，典型表现为婴儿期重症中性粒细胞减少（＜0.5×10^9/L）、反复致命性细菌感染、骨髓涂片发现中性粒细胞成熟障碍，应考虑SCN。因编码中性粒细胞弹性蛋白酶（NE）的ELA2基因为致SCN的最常见突变基因，故疑诊SCN的病人推荐首先行该基因筛查。用粒细胞集落刺激因子（G-CSF）治疗可减轻中性粒细胞减少的病程和严重程度，改善临床转归。对G-CSF无反应的病人，来自HLA-同型兄弟姐妹的造血干细胞移植是最佳治疗方式。
[Abstract]:Part I : Analysis of Clinical and Molecular Characteristics of High lgE Syndrome

Objective : To investigate the clinical and molecular characteristics of 7 cases with high lgE syndrome induced by DOCK8 gene mutation .

Methods : The clinical data of 7 children with high lgE syndrome induced by DOCK8 gene mutation were summarized , including routine blood routine , immunoglobulin level , lymphocyte classification , etiological examination , imaging examination and so on . DOCK8cDNA sequence was amplified by PCR and sequenced . The mutation type was determined by DNA exon and splice site sequencing analysis after mutation site .

Results : The high lgE syndrome caused by DOCK8 gene mutation was autosomal recessive , and was mainly characterized by atopic dermatitis , eczema , recurrent viral skin infection , respiratory tract infection including otitis media , mastoiditis , sinusitis , pneumonia and bronchitis . The clinical phenotype of this 7 children was consistent with the clinical manifestation of DOCK8 mutation - induced high lgE syndrome .

Conclusion : It is an important means to diagnose the clinical manifestation of high lgE syndrome with the mutation of DOCK8 gene . The use of antiviral drugs can improve clinical symptoms , but most of the cases are due to severe infection or skin cancer . Most of the cases should strongly consider hematopoietic stem cell transplantation . However , it is not clear whether hematopoietic stem cells are needed in patients with less severe infection .

Part Two : SCN Clinical and Molecular Characteristics Analysis

Objective : To investigate the clinical characteristics and gene mutation of an ELANE gene mutation in children with severe congenital neutropenia .

Methods : Male , 1 - year - old children were diagnosed as umbilical cord shedding ( 1 month ) , previous multiple severe bacterial infections and fungal infections ( catarrhalis and E . coli , Pseudomonas aeruginosa , Candida albicans ) . The results showed that the absolute values of peripheral blood neutrophils were lower than 0.5 脳 10 ^ 9 / L . The results showed that the absolute values of peripheral blood neutrophils were lower than 0.5 脳 10 ^ 9 / L .

Results : The mutation of exon 4 of exon 4 was found in the exon 4 of the exon 4 , which resulted in insertion of 5 amino acids ( g . 795598 _ 795599insGGACCTGCCGGC ; c . 439 _ 440insGGACCTGCCGGC ; p . 134 _ 135insAspGlnLeuproAla ) . The mother , father and brother of the child were wild - type at the site .

Conclusion : It is suggested that SCN is the most common mutation gene of SCN , and SCN is the most common mutation gene of SCN . It is suggested that SCN is the most common mutation gene in patients with SCN .

【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.9

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