{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:44:00Z","timestamp":1791218640561,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2009,9,16]],"date-time":"2009-09-16T00:00:00Z","timestamp":1253059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Von Hippel\u2010Lindau (VHL) syndrome is a dominantly inherited familial cancer syndrome caused by mutations in the <jats:italic>VHL<\/jats:italic> gene. VHL syndrome displays marked variation in expression and analysis of genotype\u2013phenotype correlations have led to the concept of four subtypes of VHL syndrome (Types 1, 2A\u2013C). Type 2 subtypes of VHL syndrome are characterized by the presence of pheochromocytoma and the three Type 2 subtypes are associated with differing risks of hemangioblastoma and renal cell carcinoma (RCC). Type 2 VHL syndrome is usually associated with surface missense mutations. Type 1 VHL syndrome is most commonly caused by germline exon deletions and truncating mutations and is characterized by susceptibility to hemangioblastomas and RCC but not pheochromocytoma. Recently, it has been suggested that large <jats:italic>VHL<\/jats:italic> gene deletions involving <jats:italic>C3orf10<\/jats:italic> (<jats:italic>HSPC300<\/jats:italic>) might be associated with a low risk of RCC. We have reviewed the molecular and clinical characteristics of 127 individuals with germline <jats:italic>VHL<\/jats:italic> gene deletions. Large <jats:italic>VHL<\/jats:italic> gene deletions associated with a contiguous loss of <jats:italic>C3orf10<\/jats:italic> were associated with a significantly lower lifetime risk of RCC than deletions that did not involve <jats:italic>C3orf10<\/jats:italic>. The risks of hemangioblastomas were similar in both groups. These results add to the growing body of evidence suggesting that patients with VHL syndrome caused by large <jats:italic>VHL<\/jats:italic> deletions that include <jats:italic>C3orf10<\/jats:italic> may be designated as having a specific subtype (Type 1B) of the disorder. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33023","type":"journal-article","created":{"date-parts":[[2009,9,17]],"date-time":"2009-09-17T01:39:03Z","timestamp":1253151543000},"page":"2147-2151","source":"Crossref","is-referenced-by-count":64,"title":["Genotype\u2013phenotype correlations in VHL exon 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