{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T06:50:22Z","timestamp":1777099822177,"version":"3.51.4"},"reference-count":13,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Cancer Institute, National Institutes of Health","award":["Contract No. HHSN261201500003I"],"award-info":[{"award-number":["Contract No. HHSN261201500003I"]}]},{"name":"Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research","award":["ZIA BC011028"],"award-info":[{"award-number":["ZIA BC011028"]}]},{"name":"Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research","award":["ZIC BC011044"],"award-info":[{"award-number":["ZIC BC011044"]}]},{"name":"Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research","award":["ZID BC011089"],"award-info":[{"award-number":["ZID BC011089"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2024,9,14]]},"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p>von Hippel-Lindau (VHL) is an autosomal-dominant hereditary tumour susceptibility disease associated with pathogenic germline variants in the <jats:italic>VHL<\/jats:italic> tumour suppressor gene. VHL patients are at increased risk of developing multiple benign and malignant tumours. Current CLIA-based genetic tests demonstrate a very high detection rate of germline <jats:italic>VHL<\/jats:italic> variants in patients with clinical manifestations of VHL. In this report, we describe a large family with canonical VHL manifestations, for which no germline alteration had been detected by conventional germline testing. We identified a novel 291\u2009kb chromosomal inversion involving chromosome 3p in affected family members. This inversion disrupts the <jats:italic>VHL<\/jats:italic> gene between exon 2 and exon 3 and is thereby responsible for the disease observed in this family.<\/jats:p>","DOI":"10.1136\/jmg-2024-110202","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T13:20:39Z","timestamp":1727184039000},"page":"1026-1030","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["A novel pathogenic germline chromosome 3 inversion in von Hippel-Lindau disease"],"prefix":"10.1136","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9256-7607","authenticated-orcid":false,"given":"Cathy D","family":"Vocke","sequence":"first","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J","family":"Ricketts","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Pack","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Raffeld","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Hewitt","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra P","family":"Lebensohn","sequence":"additional","affiliation":[{"name":"Cancer Genetic Branch, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidenys","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabindra","family":"Gautam","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krista","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura S","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"},{"name":"Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Choo","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Kenigsberg","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandeep","family":"Gurram","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily Y","family":"Chew","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naris","family":"Nilubol","sequence":"additional","affiliation":[{"name":"Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prashant","family":"Chittaboina","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria J","family":"Merino","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark W","family":"Ball","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7983-3109","authenticated-orcid":false,"given":"W Marston","family":"Linehan","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"2025101722382844000_61.11.1026.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8493574"},{"key":"2025101722382844000_61.11.1026.2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.194.3.7862955"},{"key":"2025101722382844000_61.11.1026.3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.65.6140"},{"key":"2025101722382844000_61.11.1026.4","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)12:6<417::AID-HUMU8>3.0.CO;2-K"},{"key":"2025101722382844000_61.11.1026.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00827.x"},{"key":"2025101722382844000_61.11.1026.6","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380050109"},{"key":"2025101722382844000_61.11.1026.7","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1996)8:4<348::AID-HUMU8>3.0.CO;2-3"},{"key":"2025101722382844000_61.11.1026.8","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.1.256"},{"key":"2025101722382844000_61.11.1026.9","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10302"},{"key":"2025101722382844000_61.11.1026.10","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21219"},{"key":"2025101722382844000_61.11.1026.11","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2020-107308"},{"key":"2025101722382844000_61.11.1026.12","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106519"},{"key":"2025101722382844000_61.11.1026.13","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24194"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg-2024-110202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:38:38Z","timestamp":1760765918000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg-2024-110202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,24]]},"references-count":13,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,10,23]]},"published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1136\/jmg-2024-110202"],"URL":"https:\/\/doi.org\/10.1136\/jmg-2024-110202","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,24]]}}}