Journal Article

<i>VHL</i> mutation analysis in patients with isolated central nervous system haemangioblastoma

Emma R. Woodward, Kerry Wall, Joan Forsyth, Fiona Macdonald and Eamonn R. Maher

in Brain

Published on behalf of The Guarantors of Brain

Volume 130, issue 3, pages 836-842
Published in print March 2007 | ISSN: 0006-8950
Published online January 2007 | e-ISSN: 1460-2156 | DOI:
VHL mutation analysis in patients with isolated central nervous system haemangioblastoma

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Haemangioblastomas of the CNS are a cardinal feature of von Hippel–Lindau (VHL) disease, a dominantly inherited multisystem familial cancer syndrome caused by germline mutation of the VHL tumour suppressor gene. We investigated the frequency of VHL mutations in 188 patients presenting with a single haemangioblastoma, no family history of VHL disease and no evidence of retinal or abdominal manifestations of the disease at the time of diagnosis. We found that ∼4% of patients had a detectable VHL mutation and all of these cases presented age 40 years or less. Although the identification of a germline VHL mutation has important consequences for the patient (e.g. risk of further CNS and extra-CNS tumours) and their relatives, four patients had germline VHL missense mutations [C162Y, D179N and R200W (two patients)] that may represent haemangioblastoma-only and/or low penetrance mutations. Approximately 5% of patients without a detectable VHL mutation subsequently developed a further ‘VHL type tumour’ (in most cases a further CNS haemangioblastoma). These findings suggest that a subset of patients with apparently sporadic CNS haemangioblastoma will have a germline VHL mutation but may not be at risk for developing classical VHL disease and a further group may be mosaic for a germline VHL mutation that cannot be detected in blood cells.

Keywords: genetics; haemangioblastoma; mutation; VHL

Journal Article.  3853 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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