Wiskott-Aldrich综合征1例临床及基因分析

摘要

目的：探讨Wiskott-Aldrich综合征(WAS)的WAS基因突变的特点。方法回顾分析1例WAS患儿的临床资料，以及利用PCR测序方法检测WAS基因全部外显子及侧翼序列。结果5个月男性患儿，发现血小板减少入院，既往湿疹时间长且反复感染；CD8+及CD4+ T淋巴细胞升高，CD19+ B淋巴细胞正常；骨髓细胞学提示巨核细胞成熟障碍。WAS基因检测发现存在C.880 A > G (p.Ile294Val)突变，患儿父母均未见突变。利用Polyphen2软件及SIFT软件预测该位点为致病性突变，不同物种间序列保守性分析发现该位点保守；结构预测分析发现该位点突变可能会影响正常的蛋白结构，该突变国内外未见报道。结论基因检测可早期诊断WAS，新发现C.880 A > G (p.Ile294Val)突变。%Objective To explore the characteristics of WAS gene mutation in Wiskott-Aldrich syndrome (WAS). Methods The clinical data of one infant with WAS were retrospectively analyzed. All exons and flanking sequences in WAS gene were detected by PCR. Results A 5-month-old boy, who has a history of eczema and recurrent infection, was hospitalized for thrombocytopenia. CD8+ and CD4+T cell were increased while CD19+B cell was normal. Bone marrow cytology suggested megakaryocyte mature hindrance. WAS gene detection found C.880 A > G (p.Ile294Val) mutation, but no mutations were found in parents. This site was a pathogenic mutation predicted by Polyphen 2 software and SIFT software. Besides, sequence conservation analysis of different species found it was a conservative site and structural prediction analysis revealed it may affect the normal protein structure. This site of mutation has not been reported before. Conclusions Gene detection can make early diagnosis of WAS and C.880 A > G (p.Ile294Val) is a new mutation.