{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T01:58:22Z","timestamp":1789869502523,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T00:00:00Z","timestamp":1441152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Journal of Genetic Counseling"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We present a case where a variant of uncertain significance in the von Hippel Lindau syndrome gene (<jats:italic>VHL<\/jats:italic>) was identified in a proband with haemangioblastoma, and in a second degree relative with phaeochromocytoma. Initial uncertainty due to the unclear nature of the variant created psychosocial challenges for this family, in which four other genetic conditions were also present. Subsequent RNA studies confirmed this as a novel pathogenic mutation affecting splicing of exon 2. A third relative has since been diagnosed with haemangioblastoma. We suggest that this mutation possibly has reduced penetrance as there was no history of haemangioblastoma, renal tumours (apart from small cysts) or other VHL tumours among five mutation positive and seven untested adult relatives at 50 % risk of the <jats:italic>VHL<\/jats:italic> mutation (average age 46 years, range 18\u201370 years). This case presents a novel <jats:italic>VHL<\/jats:italic> splicing mutation and highlights the psychosocial and medical value of additional laboratory studies on uncertain variants for individuals, their families and for the health professionals providing advice and counseling.<\/jats:p>","DOI":"10.1007\/s10897-015-9875-z","type":"journal-article","created":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T01:02:13Z","timestamp":1441069333000},"page":"882-889","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Novel von Hippel Lindau Gene Intronic Variant and Its Reclassification from VUS to Pathogenic: the Impact on a Large Family"],"prefix":"10.1002","volume":"24","author":[{"given":"A.","family":"Sexton","sequence":"first","affiliation":[{"name":"Familial Cancer Centre Royal Melbourne Hospital 2\u2010Centre, Grattan St Parkville VIC 3050 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Rawlings","sequence":"additional","affiliation":[{"name":"SA Pathology, Genetics &amp; Molecular Pathology Frome Rd Adelaide SA 5000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"McKavanagh","sequence":"additional","affiliation":[{"name":"SA Pathology, Genetics &amp; Molecular Pathology Frome Rd Adelaide SA 5000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Simons","sequence":"additional","affiliation":[{"name":"SA Pathology, Genetics &amp; Molecular Pathology Frome Rd Adelaide SA 5000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Winship","sequence":"additional","affiliation":[{"name":"Familial Cancer Centre Royal Melbourne Hospital 2\u2010Centre, Grattan St Parkville VIC 3050 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000159646.15026.D6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002740200"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1331-2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12097"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1897-4287-2-2-93"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.14.6459"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33139"},{"key":"e_1_2_9_9_1","volume-title":"eviQ Cancer Treatments Online 2011","author":"EviQ","year":"2014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.67.6.758"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390000265"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-11-92"},{"issue":"6","key":"e_1_2_9_13_1","first-page":"1035","article-title":"Somatic mutations of the von Hippel\u2010Lindau tumor suppressor gene and loss of heterozygosity on chromosome 3p in human glial tumors","volume":"57","author":"Kanno H.","year":"1997","journal-title":"Cancer Research"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.44"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01333.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pon.1951"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8493574"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.28.7.443"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.33.4.328"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.175"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)12:1<71::AID-HUMU14>3.0.CO;2-A"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-8-64"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21219"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20385"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1086\/302581"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/377108"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt312"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3182060456"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5413.455"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/pon.1311"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl362"}],"container-title":["Journal of Genetic Counseling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10897-015-9875-z","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T21:45:52Z","timestamp":1694814352000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10897-015-9875-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,2]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1007\/s10897-015-9875-z"],"URL":"https:\/\/doi.org\/10.1007\/s10897-015-9875-z","archive":["Portico"],"relation":{},"ISSN":["1059-7700","1573-3599"],"issn-type":[{"value":"1059-7700","type":"print"},{"value":"1573-3599","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,2]]}}}