{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:25:35Z","timestamp":1780626335402,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,1,22]],"date-time":"2004-01-22T00:00:00Z","timestamp":1074729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2004,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Generally, von Hippel\u2013Lindau (VHL) disease is caused by a germline mutation of the <jats:italic>VHL<\/jats:italic> gene (chromosome 3p), and tumorigenesis is initiated from a \u201csecond\u2010hit\u201d deletion. A subset of VHL patients have a germline deletion of the <jats:italic>VHL<\/jats:italic> gene, and the molecular events leading to tumorigenesis are not fully understood. To determine the molecular pathogenesis of tumor formation in this setting, we analyzed five central nervous system hemangioblastomas from three patients of a single VHL germline deletion kindred, all displaying mild clinical phenotype. Rather than loss of heterozygosity (the \u201csecond hit\u201d in <jats:italic>VHL<\/jats:italic> germline mutation patients), all tumors from this kindred showed \u201csecond\u2010hit\u201d point mutations on the wild\u2010type 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 \u201csecond\u2010hit\u201d 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.<\/jats:p>","DOI":"10.1002\/ana.10807","type":"journal-article","created":{"date-parts":[[2004,1,28]],"date-time":"2004-01-28T10:00:38Z","timestamp":1075284038000},"page":"236-240","source":"Crossref","is-referenced-by-count":24,"title":["Somatic mutations in <i>VHL<\/i> germline deletion kindred correlate with mild phenotype"],"prefix":"10.1002","volume":"55","author":[{"given":"Scott D.","family":"Wait","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander O.","family":"Vortmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell R.","family":"Lonser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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