嗜铬细胞瘤患者VHL基因突变的分析

Genetic detection and analysis of the VHL gene in patients with sporadic pheochromocytoma

目的探讨散发性嗜铬细胞瘤患者VHL基因突变检测及其意义。方法从41例散发性嗜铬细胞瘤患者的外周血及嗜铬细胞瘤组织中提取基因组DNA，进行VHL基因测序分析，存在基因突变者再进行家系成员筛查。以50例健康志愿者外周血提取的DNA样本作为对照。结果3例散发性嗜铬细胞瘤患者的VHL基因第2外显子存在基因突变，其中1例为572位核苷酸由G突变为C，该突变导致120位编码氨基酸由精氨酸转变为苏氨酸；2例为623位核苷酸处插入一重复核苷酸T（TTTGTtG），导致下游读码框移位。其余38例患者和50例健康志愿者未发现VHL基因突变。进一步对3例发生基因突变患者的家系成员进行筛查，分别筛查出3例G572C携带者、3例623（TTTGTtG）携带者。结论散发性嗜铬细胞瘤患者中存在可能致病的VHL基因突变，建议对散发性嗜铬细胞瘤患者进行VHL基因检测分析。VHL基因检测有望作为临床遗传性嗜铬细胞瘤基因诊断的指标之一。

Objective To carry out a genetic detection and analysis of Von Hippel-Lindau （VHL） gene in Chinese patients with sporadic pheochromocytoma. Methods DNA samples were extracted from peripheral blood cells and fresh pheochromocytoma specimens from 41 patients with sporadic pheochromocytoma were assayed by polymerase chain reaction and direct sequencing. The DNA samples of 50 healthy volunteers were extracted from peripheral blood as a control. The PCR products of exon 1, exon 2 and exon 3 were used for molecular analysis of the VHL gene. The genetic detection of family members of VHL gene mutations was also performed. Results One of mutations was located at nucleotide 572 （G→C） in exon 2, presenting a codon 120 from arginine （R） to threonine （T）. Tow small insertions were locatated at nucleotide 623T （TTTGTtG） in exon 2, leading to a frameshift mutation. There were also three carriers of G572C and three carriers of 623T （TTTGTtG） in family members of the three cases. Conclusion There are some Chinese patients with sporadic pheochromocytoma with tumorigenic VHL gene mutations. It is recommended to use the genetic detection and analysis of VHL gene as a routine examination for patients with sporadic pheoehromoeytoma under the age of 50 years with questionable family history. The genetic detection and analysis of VHL gene may be useful as a marker for the diagnosis of hereditary pheochromocytoma.