DNA-based diagnosis of the von Hippel-Lindau syndrome.

Abstract

To evaluate the etiology of a unilateral hemangioblastoma noted in a male with a family history remarkable only for spine surgery in the proband's father. Genomic DNA was isolated from peripheral blood of family members, and the three exons of the von Hippel-Lindau gene were examined for mutations by direct sequencing. A three base pair (bp) deletion in exon 1 of the VHL gene was found in the father and both sons. This in-frame deletion results in the loss of a phenylalanine residue from the von Hippel-Lindau protein product, at amino acid position 76. Genetic screening has confirmed that von Hippel-Lindau syndrome is responsible for the hemangioblastoma in the proband. Magnetic resonance imaging scans performed as a consequence of these results indicated spinal tumors present in the father and tumors present in the cerebellum of the proband's sibling. As close, lifelong follow-up is warranted with this disease, this case demonstrates the value of DNA testing in patients with ocular findings consistent with von Hippel-Lindau disease in the absence of a recognized family history.