scholarly journals A germline 1;3 translocation disrupting the VHL gene: a novel genetic cause for von Hippel-Lindau

2020 ◽  
pp. jmedgenet-2020-107308
Author(s):  
Christopher J Ricketts ◽  
Cathy D Vocke ◽  
Martin Lang ◽  
Xiongfong Chen ◽  
Yongmei Zhao ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Karyotype Analysis ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Pancreatic Cysts ◽  
Balanced Translocation ◽  
Urologic Oncology ◽  
Von Hippel Lindau ◽  
History Of ◽  
Benign Tumours

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.

scholarly journals Identification of a VHL gene mutation in atypical Von Hippel-Lindau syndrome: genotype–phenotype correlation and gene therapy perspective

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dali Tong ◽  
Yao Zhang ◽  
Jun Jiang ◽  
Gang Bi
Keyword(s):  
Gene Therapy ◽  
Gene Mutation ◽  
Suppressor Gene ◽  
Pancreatic Cysts ◽  
Vhl Gene ◽  
Von Hippel Lindau ◽  
Genetic Examination ◽  
Examination Methods ◽  
Vhl Disease ◽  
Von Hippel Lindau Syndrome

Abstract Background Classical von Hippel Lindau (VHL) disease/syndrome includes CNS hemangioblastoma, renal or pancreatic cysts, pheochromocytoma, renal carcinoma and exodermic cystadenoma. The syndrome is caused by mutation of VHL tumor suppressor gene. The most prevalent mutations are present in VHL syndrome. To date, > 500 mutations of gene related to the progression of VHL syndrome have been reported. VHL gene mutation presented in single lung or pancreatic tumor has been reported occasionally, but there is no report of both. Methods In this paper, we used CT scan, pathological and genetic examination methods to diagnose a rare atypical VHL syndrome. Results We reported a rare case of atypical VHL syndrome with authenticated VHL mutation at p.Arg167Gln, that was associated with not only bilateral pheochromocytoma but also lung carcinoid and neuroendocrine tumor of pancreas. Based on literature reviews, the patient was recommended to be further subjected to octreotide-based radionuclide therapy. Conclusions Combined with gene detection and clinical diagnosis, we found the inherent relationship between VHL genotype and phenotype, and constructed the standard diagnosis and treatment process of disease with rare VHL mutation from the perspective of gene therapy.

scholarly journals Playing Tag with HIF: The VHL Story

2002 ◽  
Vol 2 (3) ◽  
pp. 131-135 ◽  
Author(s):  
Sherri K. Leung ◽  
Michael Ohh
Keyword(s):  
Ubiquitin Ligase ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
E3 Ubiquitin Ligase ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Matrix Assembly ◽  
Von Hippel Lindau ◽  
Ubiquitin Ligase Complex

Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene product pVHL is the cause of inherited VHL disease and is associated with sporadic kidney cancer. pVHL is found in a multiprotein complex with elongins B/C, Cul2, and Rbx1 forming an E3 ubiquitin ligase complex called VEC. This modular enzyme targets theαsubunits of hypoxia-inducible factor (HIF) for ubiquitin-mediated destruction. Consequently, tumour cells lacking functional pVHL overproduce the products of HIF-target genes such as vascular endothelial growth factor (VEGF), which promotes angiogenesis. This likely accounts for the hypervascular nature of VHL-associated neoplasms. Although pVHL has been linked to the cell-cycle, differentiation, and the regulation of extracellular matrix assembly, microenvironment pH, and tissue invasiveness, this review will focus on the recent insights into the molecular mechanisms governing the E3 ubiquitin ligase function of VEC.

Molecular genetic analysis of the von Hippel-Lindau disease (VHl) tumour suppressor gene in gonadal tumours

1995 ◽  
Vol 31 (13-14) ◽  
pp. 2392-2395 ◽  
Author(s):  
K. Foster ◽  
R.J. Osborne ◽  
R.A. Huddart ◽  
N.A. Affara ◽  
M.A. Ferguson-Smith ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Molecular Genetic ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Molecular Genetic Analysis ◽  
Tumour Suppressor ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease

scholarly journals Von Hippel-Lindau disease associated with myasthenia gravis not related to thymoma

2013 ◽  
pp. 44-46
Author(s):  
Paolo Pozzato ◽  
Giovanni Sorrenti ◽  
Fabrizio Salvi ◽  
Maurizio Ventrucci
Keyword(s):  
Myasthenia Gravis ◽  
Acetylcholine Receptor ◽  
Tumour Suppressor Gene ◽  
The Body ◽  
Pancreatic Cysts ◽  
Vhl Gene ◽  
Von Hippel Lindau ◽  
Increased Risk ◽  
Von Hippel Lindau Disease ◽  
Receptor Antibodies

BACKGROUND Von Hippel-Lindau disease (VHL) is a rare autosomal dominant inherited disorder characterized by an increased risk of tumours in a number of locations (eyes, brain, adrenal gland, pancreas, liver, kidneys, or other areas of the body). It is caused by germline mutation in the VHL gene. The VHL gene is a tumour suppressor gene that has been identified on the short arm of chromosome 3. CASE REPORT We report a case of a 60 year-old female with the clinical diagnosis of VHL type 1 (cerebellar haemangioblastoma, pancreatic cysts with subsequent steatorrhoea, and bilateral renal carcinoma) who developed weakness and fatigability of skeletal muscles, left lid ptosis, snarling expression and nasal timbre speech. Acetylcholine receptor antibodies were negative in serum, while the electrodiagnostic test demonstrated an alteration of neuromuscolar junction which was consistent with the diagnosis of myasthenia gravis. Contrast-enhanced TC scan of the anterior mediastinum was performed, which excluded thymus enlargement. VHL gene evaluation in this patient identified a new mutation (c279delC9) and polymorphism c291C>G. At present the patient still suffers from ataxia and dysmetria due to cerebellar involvement in VHL, while fatigue and lid ptosis improved after the treatment with oral pyridostigmine 60 mg tid. DISCUSSION AND CONCLUSIONS To our knowledge this is the first report of a case of VHL associated with myasthenia gravis without thymoma. A case of VHL associated with a form of myasthenia gravis related to thymoma has been recently reported. In our case the absence of acetylcholine receptor antibodies may suggest a genetic origin also for the myasthenia gravis.

VON HIPPEL-LINDAU TUMOUR SUPPRESSOR GENE. LOCALIZATION OF EXPRESSION BYIN SITU HYBRIDIZATION

1996 ◽  
Vol 180 (3) ◽  
pp. 271-274 ◽  
Author(s):  
YOJI NAGASHIMA ◽  
YOHEI MIYAGI ◽  
KAORI UDAGAWA ◽  
ATSUKO TAKI ◽  
KAZUAKI MISUGI ◽  
...  
Keyword(s):  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Gene Localization ◽  
Von Hippel Lindau

scholarly journals VHL-Associated Optic Nerve Hemangioblastoma Treated with Stereotactic Radiosurgery

2018 ◽  
Vol 5 (2) ◽  
pp. 1-6 ◽  
Author(s):  
Hiroshi Kanno ◽  
Seiki Osano ◽  
Masamichi Shinonaga
Keyword(s):  
Optic Nerve ◽  
Stereotactic Radiosurgery ◽  
Rare Case ◽  
Tumor Volume ◽  
Pancreatic Cysts ◽  
Von Hippel Lindau ◽  
First Case ◽  
History Of ◽  
Fractionated Stereotactic Radiosurgery ◽  
Vhl Disease

Central nervous system hemangioblastomas are generally restricted to the cerebellum, spinal cord, and brainstem. Supratentorial hemangioblastomas are uncommon, and optic nerve hemangioblastomas are extremely rare, with fewer than 25 reports including this case. In this report, we present the case of a 36-year-old woman with von Hippel-Lindau (VHL) disease who presented with progressive diminution of vison in the left eye due to a retrobulbar optic nerve hemangioblastoma. The patient had a history of cerebellar /spinal hemangioblastomas and pancreatic cysts, and her father and brother were patients with VHL disease. Gadolinium enhanced MRI showed intraorbital retrobulbar enhanced mass on the left optic nerve. The optic nerve hemangioblastoma was treated with fractionated stereotactic radiosurgery using Novalis. Eighteen months after the stereotactic radiosurgery, the tumor volume decreased although the patient lost vision. This report presents an extremely rare case of optic nerve hemangioblastoma, which is the first case treated with stereotactic radiosurgery.

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