von-Hippel Lindau基因同义突变导致家族性嗜铬细胞瘤  

Synonymous mutations in von-Hippel Lindau gene cause familial pheochromocytoma

作　　者：马晓森 张学斌[2] 周颋[1] 崔云英[1] 童安莉[1] MA Xiao-sen;ZHANG Xue-bin;ZHOU Ting;CUI Yun-ying;TONG An-li(Department of Endocrinology,Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730,China;Department of Urology, Peking Union Medical College Hospital,CAMS & PUMC, Beijing 100730, China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院内分泌科,北京100730 [2]中国医学科学院北京协和医学院北京协和医院泌尿外科,北京100730

出　　处：《基础医学与临床》2020年第11期1489-1493,共5页Basic and Clinical Medicine

基　　金：中国医学科学院医学与健康科技创新工程项目(2017-I2M-1-001)。

摘　　要：目的报道1例罕见的VHL同义突变导致的家族性嗜铬细胞瘤家系,并探讨该突变在嗜铬细胞瘤/副神经节瘤(PPGL)中的发生频率。方法收集患者及其家系临床资料和外周血标本。提取患者外周血DNA,进行全外显子测序及生物信息学分析,并对候选变异进行一代测序验证。在另外107例PPGL患者中检测该突变的发生频率。结果先证者为15岁男性,表现为发作性心悸、大汗伴血压升高。生化检测提示去甲肾上腺素明显升高,肾上腺CT显示双肾上腺占位,手术切除后病理符合双侧嗜铬细胞瘤。家系中仅先证者姑姥姥患右侧嗜铬细胞瘤,已行手术切除肿瘤。先证者及其姑姥姥、母亲和妹妹均携带VHL同义突变c.414A>G(p.Pro138Pro)且无其他VHL病相关临床表现。并且,在另外107例PPGL中也发现一例携带相同胚系突变的患者。结论首次报道中国人中VHL同义突变导致的VHL病的家系,该突变在PPGL中的发生频率约为1%。Objective This is a case report of family with VHL disease caused by a rare synonymous mutation of VHL gene and then the frequency of the mutation in pheochromocytoma/paraganglioma(PPGL)was investigated.Methods Genomic DNA was extracted from the peripheral blood of proband and his families.The whole exome sequencing was performed to examine the potential pathogenic variations in proband and the Sanger sequencing was used to verify the mutations detected above.Results The proband was a 15-year-old male with episodic palpitations,profuse sweating and elevated blood pressure.Biochemical tests showed that 24 h urinary norepinephrine was significantly increased.CT scanning found masses in bilateral adrenal glands.The masses were removed by surgical operation and pathologically diagnosed as pheochromocytoma.In the proband's family,only the aunt of his mother suffered from pheochromocytoma,and the tumor had been surgically removed.A total of 4 family members were found to be carrier of VHL synonymous mutation c.414A>G(p.Pro138Pro).No one else in the family had other clinical manifestations of VHL disease.In addition,one patient with the same germ line mutation was also found inanother 107 cases of PPGL.Conclusions The VHL synonymous mutation is firstly reported in Chinese families.The frequency of the mutation in the PPGL cohort is about 1%.

关 键 词：双侧嗜铬细胞瘤 VHL基因 同义突变 

分 类 号：R586[医药卫生—内分泌]