Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary tumour susceptibility disease caused by germline pathogenic variation of the VHL tumour suppressor gene. Affected individuals are at risk of developing multiple malignant and benign tumours in a number of organs.
In this report, a male patient in his 20s who presented to the Urologic Oncology Branch at the National Cancer Institute with a clinical diagnosis of VHL was found to have multiple cerebellar haemangioblastomas, bilateral epididymal cysts, multiple pancreatic cysts, and multiple, bilateral renal tumours and cysts. The patient had no family history of VHL and was negative for germline VHL mutation by standard genetic testing. Further genetic analysis demonstrated a germline balanced translocation between chromosomes 1 and 3, t(1;3)(p36.3;p25) with a breakpoint on chromosome 3 within the second intron of the VHL gene. This created a pathogenic germline alteration in VHL by a novel mechanism that was not detectable by standard genetic testing.
Karyotype analysis is not commonly performed in existing genetic screening protocols for patients with VHL. Based on this case, protocols should be updated to include karyotype analysis in patients who are clinically diagnosed with VHL but demonstrate no detectable mutation by existing genetic testing.
- human genetics
- genetic testing
- cytogenetic analysis
- chromosome aberrations
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Contributors CJR, CDV and WML planed and coordinated the study. CJR, CDV, ML, XC, YZ, BT, MT, LSS, MWB and WML were involved in sequence data collection and interpretation. CJR, CDV, MWB and WML involved in clinical data collection. CJR, CDV, ML, BT, MT, LSS, MWB and WML wrote and edited the manuscript.
Funding This research was supported by the Intramural Research Programme of the NIH, NCI, Centre for Cancer Research, including grants ZIA BC011028, ZIA BC011038, ZIA BC011089 and ZIC BC011044. This project has been funded in whole or in part with federal funds from the NCI, NIH, under contract HHSN261200800001E.
Disclaimer The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government.
Competing interests None declared.
Patient consent for publication Obtained.
Ethics approval The patient’s recruitment and tissue procurement and use were approved by the Institutional Review Board of the National Cancer InstituteNCI on the NCI-97-C-0147 or NCI-89-C-0086 protocols.
Provenance and peer review Not commissioned; externally peer reviewed.
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