一个单纯家族性嗜铬细胞瘤家系的VHL基因突变筛查

Mutation screening of VHL gene in a Chinese family with nonsyndromic pheochromocytoma

目的检测一个单纯家族性嗜铬细胞瘤家系的VHL基因突变情况。方法对一个单纯家族性嗜铬细胞瘤家系进行VHL基因突变检测，抽取该家系5例患者及15名血缘亲属外周血基因组DNA，对VHL基因3个外显子进行PCR，产物进行DNA测序。结果该家系5例患者均检测出VHL基因第2外显子上第587位核苷酸A—C突变，该突变导致第125位编码氨基酸由组氨酸（H）转变为脯氨酸（P）。15名家系成员中筛查出7名成员为该突变基因携带者，B超检查发现1例为双侧肾上腺肿瘤，1例为右肾囊肿。该突变为首次报道。结论该嗜铬细胞瘤家系中检测到可能的致病突变，VHL基因检测可早期发现致病基因携带者，建议对单纯家族性嗜铬细胞瘤患者常规进行VHL基因突变筛查。

Objective To detect the VHL gene mutations in a Chinese family with nonsyndromic pheochromocytoma. Methods Mutations of VHL gene were detected in a Chinese family with nonsyndromic pheochromocytoma. Five patients and fifteen relatives were involved in this study. Peripheral blood was collected and total genomic DNA was prepared for polymerase chain reaction（PCR）. PCR products of all the three exons of VHL gene were purified and a direct gene sequence analysis was performed. Results All the five patients presented a cedon 125 from Histidine（H）to Proline （P） change at nucleotide 587 （A→C） in exon 2. Seven members of fifteen relatives were carriers with the same VHL gene mutation. Two carriers were detected with bilateral adrenal tumors and right renal cyst respectively by ultrasonic inspection. Conclusion The novel VHL gene mutation detected in this kindred may be the causative gene. Genetic test can detect the carriers in an early period. It is recommended as a routine method of genetic test in nonsyndromic pheochromocytoma patients.