2个Von Hippel-Lindau病家系调查及基因突变检测

Investigation and genetic mutations test in two Von Hippel-lindau disease kindreds

目的:探讨汉族人Von Hippel-Lindau(VHL)病临床特征及VHL基因变异情况。方法:调查2个VHL病家系临床资料,分别绘制树状图;抽取2个家族共30位成员外周血,提取基因组DNA,应用聚合酶链反应(PCR)扩增VHL基因片段并测序。将所得突变类型与人类基因突变数据库核对。结果:2个家系均以中枢神经系统血管网状细胞瘤为主要表现(13/15),部分患者呈现多脏器损害。2个家系发病年龄16～47岁,外显率为30.6%(15/49),男性发病较女性多见(13:2),术后平均6.7年复发(2～17年)。家系1共29人,4位患者及3位家族成员VHL基因第716位核苷酸G突变为C,导致第168位编码氨基酸由丝氨酸变为苏氨酸;家系2共20人,1位患者及2位家族成员VHL基因第559位核苷酸C突变为G,导致第116位编码氨基酸由亮氨酸变为缬氨酸。结论:VHL病是一种常染色体显性遗传疾病,VHL基因检测在早期发现无症状患者和致病基因携带者及对该病家族成员进行筛查方面起着重要作用。

Objective： To study the clinical characteristics and genetic mutations of Von Hippel-lindau disease.Methods： Two Chinese kindreds with Von Hippel-lindau disease were studied.DNA of 30 familial members were extracted from the peripheral blood,VHL gene sequence were detected.Then compared the mutations with the Human Gene Mutation Database.Results： The main clinical manifestation was CNS hemangioblastoma,some patients also displayed multiple organs damage.The age of onset was from 16 to 47 years old.The penetrance was 30.6%,males were of predominance.After operation,6.7 years appeared relapse.There were 29 members in the first kindred.The 716th nucleotide guanine was substituted by cytosine,which made the 168th amino acid serine substituted by threonine in four patients and three carriers.The second kindred have 20 members.Gene sequencing found the 559th nucleotide cytosine was substituted by guanine,which made the 116th amino acid leucine was substituted by valine in one patient and two carriers.Conclusion： VHL disease is autosomal dominant inheritance.The genetic testing played an important role in early detecting for asymptomatic patients and the carriers and clinical screening for members of the VHL families.