本文選題：高lgE綜合征 + DOCK8基因��； 參考：《重慶醫(yī)科大學》2012年碩士論文

【摘要】：第一部分：高lgE綜合征臨床及其分子特點分析 目的：探討7例DOCK8基因突變致高lgE綜合征患兒的臨床及分子特點。 方法：總結7例擬診為DOCK8基因突變致高lgE綜合征的患兒臨床資料，包括血常規(guī)、免疫球蛋白水平、淋巴細胞分類、病原學檢查、影像學檢查等。PCR擴增患兒DOCK8cDNA序列并雙向測序，發(fā)現突變位點后行相應DNA外顯子及拼接位點測序分析確定突變類型，并行親屬相關序列測定。 結果：DOCK8基因突變致高lgE綜合征是常染色體隱性遺傳，以生后特應性皮炎、濕疹、反復病毒性皮膚感染，呼吸道感染包括中耳炎、乳突炎、鼻竇炎、肺炎和支氣管炎，血清lgE水平明顯升高及嗜酸粒細胞血癥為主要表現。此7例患兒臨床表型均符合DOCK8突變致高lgE綜合征臨床表現。其中確診新發(fā)突變3例，除外1例，待診3例。 結論：符合DOCK8基因突變致高lgE綜合征臨床表現的患兒應行該病基因篩查及蛋白檢測，這是明確診斷的重要手段。抗病毒藥物的使用可以改善臨床癥狀，但是大部分病例因重癥感染或皮膚癌而死亡。DOCK8缺陷的重癥感染病例，應該強烈考慮造血干細胞移植，但是在感染不太重的病人是否需要造血干細胞還不明確。 第二部分：SCN臨床及其分子特點分析 目的：探討一例ELANE基因突變致重癥先天性中性粒細胞減少癥患兒及其臨床特征和基因突變。 方法：患兒男，1歲6月，，生后表現為臍帶脫落延遲（1月余），既往多次重癥細菌感染及真菌感染（卡他莫拉菌及大腸埃希菌、銅綠假單胞菌、白色念珠菌），表現為臍炎、反復呼吸道、消化道感染、皮膚感染、頸部淋巴結炎伴膿腫形成、肛周膿腫、肝臟膿腫、真菌性食道炎，行2次膿腫切開引流術及1次肝膿腫切開引流術，后因敗血癥死亡。多次查外周血中性粒細胞絕對值低于0.5×10^9/L，骨髓檢查提示粒系增生偏低，中性粒細胞成熟障礙。父系及母系家族中均無類似患者及夭折史。根據臨床表現、免疫學特征擬診為ELA2基因突變致SCN。提取患兒及父母、哥哥外周血RNA、DNA，采用PCR法擴增ELA2基因，PCR基因產物純化后進行雙向序列測定。 結果：對患兒行ELA2基因測序發(fā)現，其第4外顯子發(fā)生插入突變，導致插入5個氨基酸（g.795598_795599insGGACCAGCTGCCGGC;c.439_440insGGACCAGCTGCCGGC; p.134_135insAspGlnLeuProAla）。患兒母親、父親、哥哥在該位點為野生型。 結論：通過臨床特征及基因測序，確診1例ELA2基因突變致SCN患兒。SCN為常染色體顯性遺傳的骨髓衰竭綜合征，典型表現為嬰兒期重癥中性粒細胞減少（＜0.5×10^9/L）、反復致命性細菌感染、骨髓涂片發(fā)現中性粒細胞成熟障礙，應考慮SCN。因編碼中性粒細胞彈性蛋白酶（NE）的ELA2基因為致SCN的最常見突變基因，故疑診SCN的病人推薦首先行該基因篩查。用粒細胞集落刺激因子（G-CSF）治療可減輕中性粒細胞減少的病程和嚴重程度，改善臨床轉歸。對G-CSF無反應的病人，來自HLA-同型兄弟姐妹的造血干細胞移植是最佳治療方式。
[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 .

【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R725.9

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