并发于von Hippel-Lindau综合征的内淋巴囊肿瘤VHL基因突变检测

摘要

目的 探讨并发于yon Hippel-Lindau综合征(VHL 综合征)的内淋巴囊肿瘤(endolymphatic sac tumor,ELST)患者家庭成员VHL基因检测的临床意义.方法 调查2例伴发中枢神经系统血管瘤的ELST患者及家系资料,将获得的家系成员血样提取DNA,针对VHL基因的3个外显子进行聚合酶链反应(PCR)扩增测序.将所得突变类型与人类基因突变数据库进行核对.结果 例1家系的6人(患者及其父母和兄弟姐妹)接受了VHL基因检测,测序结果显示,例1及其妹妹和母亲VHL基因第一外显子上发现c.C194G(p.S65W)突变,其妹5年前曾在外院行视网膜血管母细胞瘤玻璃体切割手术,其母亲在随后的体检中发现小脑的血管母细胞瘤及双肾脏的实性占位.例2是独生女,对其及父母3人进行了VHL基因检测,在例2及其母亲VHL基因第三外显子发现c.C499T(p.R167W)突变,但其母亲拒绝进行进一步的检查.结论 VHL基因检测可确诊并发于VHL综合征的内淋巴囊肿瘤,对先证者家系成员的VHL基因检测可早期发现无症状的致病基因携带者,为VHL综合征家庭的遗传咨询及产前诊断提供支持.%Objective Endolymphatic sac tumors (ELSTs) are rare in the general population with much higher prevalence in yon Hippel-Lindau(VHL) disease.The purpose of this study is to present two cases of endolymphatic sac tumor with VHL disease with analysis of VHL gene and to explore their association with VHL disease using molecular analysis.Methods Clinical data of these two patients from different VHL families were studied.DNAs extracted from peripheral bloods were amplified by the polymerase chain reaction using oligonucleotide primers corresponding to the VHL gene,then compared the mutations with the Human Gene Mutation Database.Results In case 1,6 family members were enrolled in the study.Among them,three had been identified to have a germline missense point mutation at codon 194 of the VHL gene exon 1 (p.S65W).The little sister of the patient (case 1) underwent vitrectomy for retinal hemangioblastoma 5 years ago in another hospital.The mother of the patient (case 1) was further diagnosed to have a cerebellar hemangioblastoma and renal carcinoma in the following physical examination.Case 2 with her parents were also tested.Codon 499 of the VHL gene exon 3 (p.R167W) were detected in case 2 and her mother,but the mother refused further examination.Conclusions The genetic diagnosis plays an important role in early detection of symptomatic patients and suspected patients.Clinical screening for members of the VHL families,and close follow-up of carriers allow an early detection of tumors and the metastasis,which is the most common cause of death of these patients.