title: Family history of von Hippel-Lindau disease was uncommon in Chinese patients: suggesting the higher frequency of de novo mutations in VHL gene in these patients.
abstract: Von Hippel-Lindau (VHL) disease is an autosomal dominant familial cancer syndrome caused by germline mutations in VHL tumor suppressor gene. It is characterized by hemangioblastoma in central nervous system and retina, renal cell carcinoma or cyst, pheochromocytoma, pancreatic cyst and tumor, endolymphatic-sac tumor, and papillary cystadenoma in epididymis and broad ligament. Here, we used PCR-direct sequencing and universal primer quantitative fluorescent multiplex PCR (UPQFM-PCR) to detect VHL mutations in 16 patients clinically diagnosed with VHL disease. PCR-direct sequencing detected 12 germline mutations (75%, 12/16), in which a novel mutation of c.451A>T/p.Ile151Phe found in one proband had not been reported previously. UPQFM-PCR found two large deletions (12.5%, 2/16). The two remaining patients carried non-typical disease-causing mutations, including one silent mutation (c.481C>A/p.Arg161Arg) and one mutation in 3'-UTR (c.642+70C>A). Remarkably, 56.3% (9/16) probands did not have family history of VHL disease, suggesting the higher frequency of de novo mutations in Chinese patients. We also summarized Chinese VHL disease patients with VHL mutation findings published in the literature to provide information about the spectrum of VHL mutations in Chinese VHL disease patients.
authors.affiliation: Institute of Urology, Peking University, Beijing, PR China.
authors.forename: Pengjie
authors.initials: P
authors.lastname: Wu
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Xianghui
authors.initials: X
authors.lastname: Ning
authors.forename: Teng
authors.initials: T
authors.lastname: Li
authors.forename: Dingfang
authors.initials: D
authors.lastname: Bu
authors.forename: Kan
authors.initials: K
authors.lastname: Gong
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D015894:Genome, Human; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human