Somatic Mutations in VHL Germline Deletion Kindred Correlate with Mild Phenotype

Scott D. Wait, Alexander O. Vortmeyer, Russell R. Lonser, David T. Chang, Michael A. Finn, Deb A. Bhowmick, Svetlana D. Pack, Edward H. Oldfield, Zhengping Zhuang

Research output: Contribution to journalArticle

22 Scopus citations


Generally, von Hippel-Lindau (VHL) Dis. is caused by a germline mutation of the VHL gene (chromosome 3p), and tumorigenesis is initiated from a "second-hit" deletion. A subset of VHL patients have a germline deletion of the VHL gene, and the Molec. events leading to tumorigenesis are not fully understood. To determine the Molec. pathogenesis of Tum. Form. in this setting, we analyzed five Ctrl. Nerv. Syst. hemangioblastomas from three patients of a single VHL germline deletion kindred, all displaying mild Clin. phenotype. Rather than loss of heterozygosity (the "second hit" in VHL germline mutation patients), all tumors from this kindred showed "second-hit" point mutations on the wild-type allele. Moreover, in two patients who each had two hemangioblastomas resected each tumor contained a unique mutation. The specific germline deletion and the overall genetic makeup of the patient did not predict these random "second-hit" point mutations. These results suggest that in patients with germline deletion of a tumor suppressor gene there is a unique genetic mechanism underlying tumorigenesis. This unique genetic mechanism correlates with and may help to understand the mild clinical phenotype seen in these patients.

Original languageEnglish (US)
Pages (from-to)236-240
Number of pages5
JournalAnnals of Neurology
Issue number2
StatePublished - Feb 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Wait, S. D., Vortmeyer, A. O., Lonser, R. R., Chang, D. T., Finn, M. A., Bhowmick, D. A., Pack, S. D., Oldfield, E. H., & Zhuang, Z. (2004). Somatic Mutations in VHL Germline Deletion Kindred Correlate with Mild Phenotype. Annals of Neurology, 55(2), 236-240.