6例Wiskott—Aldrich综合征患儿的临床特点和基因分析  

Analysis of clinical features and gene mutations in 6 patients with Wiskott-Aldrich syndrome

作　　者：江明华[1] 王兆钺[1] 苏健[1] 曹丽娟[1] 李建琴[1] 孙雄华[1] 白霞[1] 王改锋[1] 阮长耿[1] 

机构地区：[1]苏州大学附属第一医院、江苏省血液研究所,卫生部血栓与止血重点实验室,215006

出　　处：《中华血液学杂志》2011年第9期577-582,共6页Chinese Journal of Hematology

基　　金：国家自然科学基金（81070395）

摘　　要：目的分析6例Wiskott—Aldrich综合征（WAS）患儿的临床特点、实验室检测指标改变特征及基因突变，探讨其临床与病理意义。方法用流式细胞术检测WAS患儿T细胞亚群；免疫浊度法分析患儿免疫球蛋白；全血分析仪检测患儿外周血白细胞、红细胞及血小板等；用PCR结合直接测序方法分析患儿及其父母WAS蛋白（WASP）基因。结果患儿均反复感染及发生湿疹，临床评分为3或4分。患儿血小板计数均减少伴平均血小板体积减少，均有轻中度贫血，白细胞计数有所升高；骨髓检查示巨核细胞数正常或轻度增加，伴成熟障碍，产血小板能力下降。患儿CD3＋T细胞减少，CD4＋／CD8＋比值紊乱，CD19＋及CD16＋CD56＋细胞均正常；患儿IgA均增高，IgG大多数增高，1例IgM增高。6例患儿中发现了6种基因突变：10250C—T，6783C—G，10216—10221插入G，9964缺失T，10192—10203缺失GCCTGCCGGGG与10052—10059缺失GCTACTG。后5种为新的突变；例1、2、3、4患儿的母亲为相应突变携带者，而P5与P6患儿母亲不携带相应的突变，属散发性病例。除6783C—G（Y102stop）位于外显子3，其余突变位于外显子10，均为无义、小插入或缺失突变。结论本组WAS患儿血小板计数减少伴小血小板，免疫功能紊乱；基因突变均为缺失、插入及无义突变，其临床表型与基因突变类型有一定关系；患儿都曾被误诊为原发免疫性血小板减少症，鉴别诊断具有重要意义。Objective To investigate clinical features, laboratory alterations and gene mutations of 6 patients with Wiskott-Aldrich syndrome （WAS）. Methods T lymphocyte subtypes were measured by flow cytometer. The routine blood tests including platelet count and mean platelet volume were performed by com- plete blood analyzer Sysmex XE2100. Serum immunoglobulin was measured by immunoturhidimetry. Mutations in WAS protein （WASP） gene （including all the exons and exon-intron boundaries and 3＇, 5＇ untransla- tion region） of 6 patients and their family members were identified by PCR and sequencing. Results The patients presented with peteehiae, easy bruise, eczema, bloody diarrhea, recurrent infection and fever, and the clinical scores were 3 or 4. They were thrombocytopenia with smaller mean platelet volume, anemia and leukoeytosis. Megakaryocyte number was normal or slightly increased in bone marrow. In the probands, the percentage of CD3 ＋ T cells was decreased, the CD4＋/CD8＋ ratio was abnormal, while the fractions of CD19 ＋ and CD16 ＋ CD56 ＋ cells were in normal range. In most of the patients, the serum levels of IgG and IgA were increased. Six mutations were identified in the patients, including 10250 C→T, and five novel mutations＇： 6783 C→G,10216-10221 Ins G, 9964 Del T,10192-10203 Del GCCTGCCGGGG and 10052-10059 del GCTACTG. The 6783 C→G in exon 3 resulted in premature stop at Tyrl02, and the remaining four mutations in exon 10 resulted in frame shift and premature stop. Conclusion The main characteristics of these WAS patients were thrumbocytopenia with smaller mean platelet volume and immunological disturbance. Their gene mutations were deletion, insertion or nonsense mutations. All the patients had been misdiagnosed as ITP, indicating the importance of differential diagnosis.

关 键 词：WISKOTT-ALDRICH综合征 基因分析 血小板 

分 类 号：R725.9[医药卫生—儿科]