CAJ | 학술논문

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:10250 C→T，6783 C→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。
목적 분석6례Wiskott-Aldrich종합정(WAS)환인적림상특점、실험실검측지표개변특정급기인돌변，탐토기림상여병리의의。방법 용류식세포술검측WAS환인T세포아군;면역탁도법분석환인면역구단백;전혈분석의검측환인외주혈백세포、홍세포급혈소판등;용PCR결합직접측서방법분석환인급기부모WAS단백(WASP)기인。결과 환인균반복감염급발생습진，림상평분위3혹4분。환인혈소판계수균감소반평균혈소판체적감소，균유경중도빈혈，백세포계수유소승고;골수검사시거핵세포수정상혹경도증가，반성숙장애，산혈소판능력하강。환인CD3+T세포감소，CD4+/CD8+비치문란，CD19+급CD16+ CD56+세포균정상;환인IgA균증고，IgG대다수증고，1례IgM증고。6례환인중발현료6충기인돌변:10250 C→T，6783 C→G，10216-10221삽입G，9964결실T，10192-10203결실GCCTGCCGGGG 여10052-10059결실GCTACTG。후5충위신적돌변;례1、2、3、4환인적모친위상응돌변휴대자，이P5여P6환인모친불휴대상응적돌변，속산발성병례。제6783C→G(Y102stop)위우외현자3，기여돌변위우외현자10，균위무의、소삽입혹결실돌변。결론 본조WAS환인혈소판계수감소반소혈소판，면역공능문란;기인돌변균위결실、삽입급무의돌변，기림상표형여기인돌변류형유일정관계;환인도증피오진위원발면역성혈소판감소증，감별진단구유중요의의。
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 complete blood analyzer Sysmex XE2100. Serum immunoglobulin was measured by immunoturbidimetry. Mutations in WAS protein(WASP) gene (including all the exons and exon-intron boundaries and 3＇, 5＇ untranslation region) of 6 patients and their family members were identified by PCR and sequencing. Results The patients presented with petechiae, 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 leukocytosis. 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 10052-10059del GCTACTG. The 6783 C→G in exon 3 resulted in premature stop at Tyr102, and the remaining four mutations in exon 10 resulted in frame shift and premature stop. Conclusion The main characteristics of these WAS patients were thrombocytopenia 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.