24例Wiskott-Aldrich综合征患儿基因型与临床表现型的关系  

Genotype and phenotype correlation of Wiskott-Aldrich syndrome:a report based on 24 Chinese patients

作　　者：赵琴[1] 蒋利萍[1] 于洁[1] 肖剑文[1] 赵晓东[1] 

机构地区：[1]重庆医科大学附属儿童医院肾脏免疫科,重庆400014

出　　处：《第三军医大学学报》2011年第13期1404-1407,共4页Journal of Third Military Medical University

基　　金：重庆市杰出青年科学基金(CSCT2008BA5040)~~

摘　　要：目的分析24例Wiskott-Aldrich综合征(Wiskott-Aldrich syndrome,WAS)患儿基因型与临床表现型关系。方法收集24例WAS患儿临床资料,进行临床表现型评分。流式细胞术检测患儿外周血单个核细胞(peripheral bloodmononuclear cells,PBMCs)、WAS蛋白(Wiskott-Aldrich syndrome protein,WASP)的表达。对WASP基因进行直接测序,并分析基因型与表现型的关系。结果 24例患儿系男性,2例临床表现型评分为2分,为X连锁血小板减少症(X-linkedthrombocytopenia,XLT);其余患儿评分均≥3分,为典型WAS。除1例WASP正常表达,2例WASP表达减少外,其余患儿WASP均为阴性。发现WASP基因突变包括7例错义突变、4例无义突变、6例缺失突变及7例拼接位点突变。共发现基因突变21种、新发突变3种,即180 C>T(A49V)、342-343del CA(S103fsX121)、IVS7+2 T>C。发现已报道的热点突变6种,包括291 G>A(R86H)、291G>T(R86L)、1035del G(G334fsX444)、665 C>T(R211X)、IVS6+5 G>A、IVS8+1 G>A。错义突变患儿2例为XLT,其余均为典型WAS。无义突变、缺失突变及拼接位点突变的患儿均为评分3～5分的典型WAS,部分患儿表现型严重。结论 WASP下游区域的基因突变、无义、缺失、拼接位点突变类型则更可能导致WASP表达缺失、不稳定或截短型WASP,临床表型多为典型WAS。环境因素可导致患儿表现型加重。Objective To study genotype-phenotype correlation preliminarily in 24 Chinese Wiskott-Aldrich syndrome（WAS） patients.Methods Clinical data of 24 Chinese male WAS patients from 21 unrelated families were collected,then patients＇ phenotypes were scored according to international scoring standards.Flow cytometry was used to analyze WAS protein（WASP） expression in peripheral blood mononuclear cells（PBMCs）.WASP gene was directly sequenced,then the genotype-phenotype correlation was analyzed.Results Among the 24 patients,2 of them were X-linked thrombocytopenia（XLT）with scores 2,and the others were classic WAS with scores 3 to 5.WASP of 1 patient was of normal expression,that of 2 was of reduced expression,and that of the others was of negative expression.We had found 7 missenses,4 nonsenses,6 deletions,and 7 splice site mutations.Among 21 detected unique mutations,there were 3 novel mutations,that is,180 C〉T（A49V）,342-343del CA（S103fsX121） and IVS7＋2 T〉C.There were 6 hot spot mutations were reported which were 291 G〉A（R86H）,291GT（R86L）,1035del G（G334fsX444）,665 C〉T（R211X）,IVS6＋5 G〉A and IVS8＋1 G〉A.Two of all missense mutation patients were XLT,the others were classic WAS.All nonsense,deletion and splice site mutations patients were classic WAS,some of whose phenotype were severe.Conclusion Mutations in downstream of WASP gene,nonsense,deletion and splice site mutations probably lead to negative expression of WASP,unstable or trancated WASP production,with typical clinical manifestations of WAS.What＇s more,environmental affections might worsen patients phenotypes.

关 键 词：WISKOTT-ALDRICH综合征 WASP表达 基因型 临床表现型 

分 类 号：R725.5[医药卫生—儿科] R725.96[医药卫生—临床医学]