Wiskott-Aldrich综合征家系调查及基因突变分析

目的：对一个Wiskott-Aldrich综合征家系进行调查，并对候选突变基因WASP进行分析，探讨该病临床特点和发病机制。方法一例3代人Wiskott-Aldrich 综合征家系，调查家系14名成员病史，采集外周血样并提取DNA，采用PCR扩增、DNA直接测序技术进行WASP基因突变分析。结果 PCR-DNA直接测序证实先证者WASP基因2号外显子291号碱基G/A突变，导致该基因第86号氨基酸由精氨酸（R）变为组氨酸（H），即WASP基因R86 H错义突变。家系中患者检出与先证者相同的突变，患者母亲均为突变携带者。结论 Wiskott-Aldrich综合征是X连锁隐性遗传病，X连锁血小板减少症是Wiskott-Aldrich综合征的一种轻型表现，WASP基因突变是该病的分子学发病机制。本研究发现的R86H突变是Wiskott-Aldrich综合征的热点突变位点。Wiskott-Aldrich综合征临床上缺乏特征性诊断依据，对该病认识的提高和基因诊断有助于早期识别和正确诊断。

The WASP gene mutation analysis of a family of Wiskott-Aldrich syndrome

Objective This study investigated the history and WASP gene mutation of the family with Wiskott-Aldrich syndrome,thus to understand the clinical characteristic and molecular pathogenesis of this disease.Methods A three-generation Wiskott-Aldrich syndrome family was investigated.Family history and peripheral blood sample was collected from the 13 family members.Polymerase chain reaction （PCR）-DNA direct sequencing was done to screen all exons of WASP gene for mutation analysis. Results PCR and subsequent direct sequencing of WASP found a missense mutation （G→A）at 29 1 bp of exon 2,corresponding to amino acids Arg （R）86 changes to His（H）,and this is the R86H missense mutation of WASP.In patient of the family found the same mutation.All the patients’mothers were the carrier of the mutation. Conclusions Wiskott-Aldrich syndrome was X-linked recessive disorder. X-linked thrombocytopenia was one mild phenotype of this syndrome.WASP mutation was the molecular mechanism of X-linked thrombocytopenia.To our knowledge,R86H of WASP was a hot spot for the disease.Because there was no much characteristic of clinical manifestation,Wiskott-Aldrich syndrome should be recognized earlier and diagnosed correctly by genomic methods, and depended on the knowledge of the doctors.