00422386

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von Hippel-Lindau病患者の遺伝子異常と表現型

Genetic analysis and phenotype in von Hippel-Lindau disease

Medical journal of Kobe University

65(1/2/3/4)

35-42

神戸大学医学会

2005-03

2008-10-10

本文ファイルは、国立情報学研究所CiNiiより提供されたものです。

Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome, characterized by retinal, spinal, and cerebellar haemangioblastomas, clear cell renal carcinomas, phaeochromocytomas, pancreatic tumors, and endolymphatic sac tumor that is associated with a germ line mutation of the VHL gene. We performed genetic analysis in patients with VHL disease and their family members, and identified 4 different mutations of the VHL gene. As described previously, patients with nonsense mutation at the region encoding the β sheet showed type 1 VHL disease without pheochromocytoma (PHE) whereas those with missense mutation at the region encoding the α domain showed type 2 phenotype with PHE. In addition, we identified a novel missense mutation (P154S) in family 1. It is of interest that one of the family members showed hepatic hemangiomas (HH) as well as PHE. Although HH is not reported as a phenotype of VHL disease so far, heterozygous vhl gene disrupted mice (vhl+/-mice) demonstrated HH, suggesting that HH may be one the phenotype of VHL disease even in human. Codon 154 is located at the boundary between α and β domain of the VHL protein. In summary, the finding in our patients suggests that HH may be one of the phenotype of human VHL disease and may provide novel information about genotype-phenotype correlation in terms of hepatic hemangioma in human VHL disease.

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