一VHL 家系致病基因突变的检测与分析*

目的:研究中枢神经系统血管母细胞瘤(VHL)基因突变的主要类型和发生情况,探讨VHL疾病发生的原因、临床特点等。方法:以基因组DNA为模板,PCR扩增VHL基因3个外显子及5’UTR区域,结合DNA直接测序的方法,对一个有多个小脑血管母细胞瘤患者的家系进行VHL基因突变检测。结果:发现该家系VHL基因5’UTR区、外显子1和外显子2正常,外显子3存在c.499C>G的改变,为一个错意突变,氨基酸改变为Arg-Gln(p.R167Q),该突变是导致这个家系的患者发病的直接原因。结论:VHL疾病的突变主要集中在VHL蛋白的α、β结构域,位于α结构域的p.R167Q突变为该VHL家系致病的主要原因。

Identification and Analysis of Mutations in VHL Patients*

Objective: To determine characters and distributions of VHL gene mutations and discuss the pathogenic,clinical characteristics,diagnosis and treatment progress of VHL disease.Methods: Using genome DNA PCR(polymerase chain reactions) amplify all 3 exons of VHL gene and 5’UTR(un-transcribed region).PCR products were analyzed and sequenced.Results: There are no mutations in exon 1 and exon 2 of VHL.A missense mutation c.499C>G(p.R167Q) in exon 3 was identified to lead to the onset of the VHL family by DNA sequencing.Conclusions: Mutations of VHL gene are mainly found in the α β function domain.Mutation of p.R167Q is the reason for the VHL patients.