一个血小板平均体积正常的Wiskott—Aldrich综合征家系调查及基因突变分析

The gene mutation analysis of a Wiskott-Aldrich syndrome family with normal mean platelet volume

目的调查1个血小板平均体积（MPV）正常的Wiskott-Aldrich综合征（WAS）患者家系资料，分析先证者及其母亲WASP基因突变情况，探讨WAS的临床特征。方法以1个四代共22人WAS家系为研究对象，调查该家系成员病史，采集先证者及母亲外周血标本并提取DNA，采用一代基因测序进行WASP基因全部外显子突变分析。结果先证者及其哥哥MPV均正常。先证者WAS临床评分5分，抗PM-Scl抗体阳性，抗PCNA抗体阳性，抗核糖体P蛋白抗体阳性，抗链球菌溶血素明显增高。先证者合并有自身免疫性疾病、贫血、肾功能异常、真菌感染及巩膜炎。先证者WASP基因2号外显子173号碱基C〉T纯合突变，导致第58号氨基酸由脯氨酸异变为亮氨酸。先证者母亲为WASP突变携带者。先证者CBL、CREBBP、DNM2及ADAMTS13基因突变频率明显高于正常人群。结论该例WAS患者WASP基因173C〉T突变，无湿疹，MPV正常，伴有自身免疫性疾病，为国内首次报道；其母亲为WASP突变携带者。WAS基因突变检测有助于早期识别和确诊WAS。

Objective To investigate the history of a Wiskott-Aldrich syndrome （WAS） family with normal mean platelet volume （MPV）, analyse the WASP gene mutation of to better understand its clinical characteristics. Methods A four-generation WAS family histories of 22 members were investigated. Peripheral blood samples were collected from propositus and his mother to analyse all exon mutations of WASP gene using sanger sequencing. Results The MPV of both propositus and his elder brother were normal. The patient＇ s clinical score was 5, antibodies to PM-Scl, PCNA and PO were positive with very high level of ASO, the patient co-suffered from autoimmune disease, anemia, abnormal renal function, fungal infection and scleritis. A homozygous mutation （C 〉 T） was found at 173 bp of exon 2, corresponding to amino acids Pro （P） 58 abnormally changed to Leu （L）. His mother was the carrier of the mutation. Of 112 blood diseases-related genes, mutation frequencies of CBL, CREBBP, DNM2 and ADAMTS13 were higher than normals. Conclusions This was the first report the phenotype 173C〉T mutation of WASP without eczema, but with normal MPV and autoimmune disease in Chinese, WAS should be recognized earlier and diagnosed correctly by genomic methods.