Mutational Research of von Hippel-Lindau Gene of Family with von Hippel-Lindau Disease

Eom, Ki Seong; Kim, Tae Young; Kim, Jong Moon

Abstract

OBJECTIVE
The von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by deletions or mutations in a tumor suppressor gene on human chromosome 3p25. We investigate the VHL germline mutations in a family with VHL disease to define the role of molecular genetic analysis in the management of such patients. And our data add to the diversity of VHL germ-line mutations and provide a better understanding of VHL disease in terms of both clinical management and molecular pathogenesis. METHODS: We have experienced two cases of VHL disease in a family. A 18-year-old male had multiple scattered hemangioblastomas in cerebellum and spinal cord, retinal angiomas and renal cyst. And his mother had a renal cell carcinoma in addition to a solid type hemangioblastoma in cerebellum. The genomic DNA was isolated from peripheral blood cell of family members and renal cell carcinoma of affected mother, and amplified the three exons (acidic domain: aa 1-63, beta domain: aa 64-153, alpha domain: aa 154-213) of VHL suppressor gene to verify the sequences mutations. RESULTS: The data showed that the family with VHL disease does not have any notable mutation in three exons of VHL tumor suppressor gene in both peripheral blood and renal cell carcinoma. CONCLUSION: The failure to detect germline VHL mutations in family with VHL disease may indicate the presence of somatic mosaicism or additional susceptibility genes. Further studies are required to elucidate the mechanism how the VHL disease is induced without any notable mutational inactivation.