title: p.N78S and p.R161Q germline mutations of the VHL gene are present in von Hippel-Lindau syndrome in two pedigrees.
abstract: Von Hippel-Lindau (VHL) disease is an autosomal dominant familial cancer syndrome. VHL is characterized by the development of renal cell carcinoma (RCC), hemangioblastomas of the central nervous system or retina and pheochromocytoma (PCC). RCC and PCC are known to be caused by germline mutations of six and ten genes, respectively. In the present study, 30 individuals from two unrelated pedigrees with type 2A and 2C VHL syndrome were investigated. The patients were clinically examined and treated by radical nephrectomy [or nephron‑sparing surgery (NSS)] and cortical-sparing adrenalectomy (CSA), and all members of the two families underwent genetic screening. Two members from the first family were diagnosed with PCC and RCC, and three individuals from the second family who had only hypertension were diagnosed with PCC. Heterozygous variants of the VHL gene, c.A233G (p.N78S) within exon 1 and c.G482A (p.R161Q) within exon 3, were verified, respectively. Surgery was performed on all the patients, with the exception of an asymptomatic 5-year-old p.N78S male in family 1, in addition to genetic testing and genetic counseling. Further patient follow-up was warranted with regard to blood pressure and health, although normal blood pressure and no local recurrence and distant metastasis of VHL were observed previously. The present study suggests that molecular genetic testing may aid the diagnosis and clinical management of VHL syndrome.
authors.affiliation: Department of Urologic Surgery, The 117th PLA Hospital, Hangzhou, Zhejiang 310013, P.R. China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Qi
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Liu
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Dai
authors.forename: Ju-Ming
authors.initials: JM
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Fei
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Mao
authors.initials: M
authors.lastname: Shen
authors.forename: Hang-Yang
authors.initials: HY
authors.lastname: Jin
authors.forename: Zhen-Guang
authors.initials: ZG
authors.lastname: Chen
authors.forename: Zhen-Fang
authors.initials: ZF
authors.lastname: Du
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Chen
authors.forename: Xian-Ning
authors.initials: XN
authors.lastname: Zhang
mesh_terms: D000315:Adrenalectomy; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D005817:Genetic Counseling; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D010375:Pedigree; D017422:Sequence Analysis, DNA; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human