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Von Hippel Lindau disease (VHL) is a monogenic disorder characterized by the development of tumors affecting the central nervous system, kidney, pancreas, or adrenal glands, and due to germline mutations in the VHL tumor suppressor gene. About 5% of patients harboring a typical VHL phenotype have no mutation detected by conventional techniques, so a postzygotic VHL mosaicism can be suspected. The aim of this study was therefore to implement a next-generation sequencing (NGS) strategy for VHL mosaic mutation detection, including an optimization of the original Personal Genome Machine design by enrichment with oligonucleotides corresponding to amplicons with insufficient depth of coverage. Two complementary strategies were developed for the confirmation of mosaic mutations identified by NGS, SNaPshot for variants present at an allelic ratio greater than 5%, and droplet digital PCR for allelic ratio above 1%. VHL mutant plasmids were generated to assess VHL mosaic mutation detection in different exons and to set up an internal quality control that could be included in each run or regularly to validate the assay. This strategy was applied to 47 patients with a suggestive or clinical VHL disease and mosaic mutations were identified in 8.5% of patients. In conclusion, NGS technologies combined with SNaPshot or droplet digital PCR allow the detection and confirmation of mosaic mutations in a clinical laboratory setting.
This article was published in the following journal.
Name: The Journal of molecular diagnostics : JMD
To detect VHL gene mutation in a pedigree affected with von Hippel-Lindau syndrome (VHL).
von Hippel-Lindau disease, comprising renal cancer, hemangioblastoma and/or pheochromocytoma (PHEO) is caused by missense or truncating variants of the VHL tumor suppressor gene, which is involved in ...
We reviewed the feasibility and safety of nephron sparing surgery for renal cell carcinoma in patients with von Hippel Lindau (VHL) disease.
Von-Hippel Lindau (VHL) disease is rare neurocutaneous disorder arising from an inactivating mutation of the VHL gene on chromosome 3p35. The disease is inherited in an autosomal dominant fashion and ...
RATIONALE: The identification of gene mutations in individuals who have or are at risk for von Hippel-Lindau syndrome may allow doctors to better determine the genetic processes involved i...
The purpose of this study is to determine whether PTK787/ZK 222584 is effective in treating hemangioblastoma of the brain and/or retina in patients with von Hippel-Lindau disease. The stud...
The purpose of this study is to determine if contrast-enhanced ultrasound can detect abnormal features of kidney lesions in patients with Von-Hippel Lindau with the same accuracy as conven...
This study is designed to investigate PT2977 as a treatment for VHL disease associated RCC.
RATIONALE: Genetic studies may help in understanding the genetic processes involved in the development of some types of cancer. PURPOSE: Genetic study to determine how reproductive, hormo...
A ubiquitin-protein ligase that mediates OXYGEN-dependent polyubiquitination of HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. It is inactivated in VON HIPPEL-LINDAU SYNDROME.
An autosomal dominant disorder caused by mutations in a tumor suppressor gene. This syndrome is characterized by abnormal growth of small blood vessels leading to a host of neoplasms. They include HEMANGIOBLASTOMA in the RETINA; CEREBELLUM; and SPINAL CORD; PHEOCHROMOCYTOMA; pancreatic tumors; and renal cell carcinoma (see CARCINOMA, RENAL CELL). Common clinical signs include HYPERTENSION and neurological dysfunctions.
A benign tumor of the nervous system that may occur sporadically or in association with VON HIPPEL-LINDAU DISEASE. It accounts for approximately 2% of intracranial tumors, arising most frequently in the cerebellar hemispheres and vermis. Histologically, the tumors are composed of multiple capillary and sinusoidal channels lined with endothelial cells and clusters of lipid-laden pseudoxanthoma cells. Usually solitary, these tumors can be multiple and may also occur in the brain stem, spinal cord, retina, and supratentorial compartment. Cerebellar hemangioblastomas usually present in the third decade with INTRACRANIAL HYPERTENSION, and ataxia. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2071-2)
The type species of TOBAMOVIRUS which causes mosaic disease of tobacco. Transmission occurs by mechanical inoculation.
A unit of the National Institutes of Health that seeks to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. The Center was established in 2011.
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. During DNA sequencing, the bases of a small fragment of DNA are sequentially identified from signals emitted as each fragment is re-synthesized from a ...
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...