Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Von Hippel Lindau disease (VHL) is a hereditary syndrome, associated with tumors and cysts in multiple organ systems, whose expression and age of onset are highly variable. The availability of a genetic test for the early and reliable detection of individuals carrying the defective gene would be beneficial for VHL patients and their relatives, since many of the manifestations of VHL can be successfully treated if detected in their early stages, while the complications of undetected disease can be devastating. We have previously shown that the VHL gene maps to chromosome 3p. To provide genetic markers for the development of a reliable diagnostic test, and to further narrow and eventually clone the VHL defect, we have generated DNA markers for chromosome 3p. With these markers, we have performed a multipoint genetic linkage analysis in 28 VHL pedigrees, comprising 470 individuals, 164 of whom were affected with VHL. Here we report the identification of tightly linked markers, including flanking markers that bracket the VHL gene to a small region on chromosome 3p25-p26. This finding has several major implications. While visceral cysts of the kidney, pancreas, and epididymis are commonly found in VHL and are considered diagnostic criteria for this disorder, they also occur in the general population. The presence of cysts, unaccompanied by other more typical lesions such as retinal and cerebellar hemangioblastoma, may therefore represent a major diagnostic problem, leading to errors in the assessment of disease status. The application of flanking markers for the VHL gene for presymptomatic diagnostic testing confirms that epididymal cysts are indeed not suitable as a diagnostic criterion in this disorder. Pheochromocytomas occur nonuniformly in VHL families and may also be associated with other hereditary tumor syndromes; our genetic studies imply that the phenotype in VHL families with and without pheochromocytomas is caused by defects within the same gene. The absence or presence of this tumor type is therefore due to the pleiotropic expression of a single gene rather than to the existence of several different genes for VHL. The region on chromosome 3p13-p14 known to contain several chromosomal translocation breakpoints in families with "pure familial renal cell carcinoma" is quite proximal to the VHL locus in 3p25-p26 we have identified. Chromosome 3p may therefore contain two loci for renal cell carcinoma: one gene (or genes) in 3p13-p14 and the VHL gene in 3p25-p26, whose aberration is also associated with other typical manifestations of VHL. Since renal cell carcinoma, pheochromocytoma, and visceral cysts can occur sporadically even in young people and may also be associated with other tumor syndromes, the availability of flanking markers for the VHL gene will be useful in identifying VHL gene carriers, particularly among those individuals at risk in whom these are the only manifestations of disease. The isolation and characterization of the VHL gene, based on the identification of flanking markers, will have important implications for diagnosis and treatment of patients with VHL, as well as for a much larger number of individuals having the sporadic counterparts of VHL-associated tumor types.
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PMID:Genetic flanking markers refine diagnostic criteria and provide insights into the genetics of Von Hippel Lindau disease. 201 96

Common manifestations of the von Hippel-Lindau syndrome, an autosomally dominant inherited cancer-prone disorder, include retinal angiomatosis, hemangioblastoma of the central nervous system, renal cysts, renal cancer, pheochromocytoma, and epididymal cystadenoma. Multiple cysts and microcystic (serous) cystadenomas of the pancreas have also been reported occasionally in patients afflicted with this syndrome. In the large Freiburg study of the von Hippel-Lindau syndrome composed of 66 affected individuals, pancreatic lesions were systematically studied. Fifty-five living individuals were examined by abdominal ultrasound imaging. Abnormal findings were confirmed by computed tomographic scan and/or magnetic resonance imaging. For an additional 11 decreased patients autopsy data were available. Cystic lesions of the pancreas were found in 10 patients (15%). One of these patients presented with multiple pancreatic cysts as the only manifestation of the syndrome. In one patient, a malignant islet-cell tumor was found at autopsy. Because multiple pancreatic cysts did not cause major clinical symptoms and because follow-up examinations over an average period of 5 years did not show significant progression of the lesions, it is concluded that these patients usually do not require surgical treatment. Abdominal ultrasound screening is recommended for patients at risk as a tool to identify potential von Hippel-Lindau syndrome gene carriers with pancreatic manifestations. In all patients with multiple pancreatic cysts, the von Hippel-Lindau syndrome should be included in the differential diagnosis.
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PMID:Pancreatic lesions in the von Hippel-Lindau syndrome. 206 22

We report a case of bilateral papillary cystadenoma of the epididymis thought to be a component of the von Hippel-Lindau syndrome. The patient was hospitalized initially because of infertility. He had undergone a craniotomy 2 years previously for the diagnosis of a cerebellar hemangioblastoma. Funduscopy had revealed angiomatous lesions of the left eye. The von Hippel-Lindau syndrome is discussed briefly and the importance of long-term urological followup for possible presentation of silent renal carcinoma is emphasized. Patients with bilateral epididymal papillary cystadenoma are prone to have other components of the von Hippel-Lindau syndrome, and clinical studies are indicated in all such patients.
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PMID:Bilateral papillary cystadenoma of the epididymis as a component of von Hippel-Lindau's syndrome: report of a case presenting as infertility. 396 52

After a decade of intensive clinical and molecular genetic efforts the von Hippel-Lindau (VHL) gene was cloned in 1993. The open reading frame encodes the putative protein of 284 amino acids. A large number of different mutations have been identified so far, including single base mutations, deletions, rearrangements and more complex mutations. So far, in about 75% of the VHL families germline mutations were detected. Geno-phenotypic comparison has revealed specific mutations with distinct manifestation patterns. Not all of the 6 classical lesions (hemangioblastoma of the CNS, retinal angiomatosis, pancreatic cysts, renal cysts and carcinoma, pheochromocytoma and epididymal cystadenoma) are present in VHL families. Pedigrees with pheochromocytoma but without renal cancer in general have point mutations. These recent results provide insight in the pathogenesis of a multiorgan cancer susceptibility tumor suppressor gene and allow determination of carrier status.
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PMID:Von Hippel-Lindau syndrome. 767 Jun 59

Vascular endothelial growth factor (VEGF) is a hypoxia inducible angiogenic and vascular permeability factor. Although VEGF expression in glioblastoma is induced by hypoxia, its expression in renal cell carcinoma and hemangioblastoma is thought to be related to mutation of the von Hippel-Lindau (VHL) gene. It is not certain whether other lesions in VHL syndrome are associated with an elevated VEGF level. We report a VHL syndrome patient with multiple hemangioblastomas and bilateral epididymal clear cell papillary cystadenomas. In situ hybridization revealed high levels of VEGF mRNA in the clear cells of the epididymal tumor and the stromal cells of the hemangioblastoma. This lends support to the notion that upregulation of VEGF is caused by loss of the wild-type VHL protein. We postulate that the elevated VEGF levels may account for the cyst formation and vascularized stroma present in these VHL-associated tumors.
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PMID:Expression of vascular endothelial growth factor in von Hippel-Lindau syndrome-associated papillary cystadenoma of the epididymis. 982 15

Von Hippel-Lindau (VHL) syndrome (OMIM 193300) is an autosomal dominant disorder caused by deletions or mutations in a tumor suppressor gene mapped to human chromosome 3p25. It is characterized clinically by vascular tumors, including retinal and central nervous system hemangioblastomas (cerebellar, spinal, and brain stem). Hemangioblastomas are benign and do not metastasize. Other features include cysts of the kidneys, liver, and pancreas. Clear cell renal cell carcinoma occurs in up to 70% of patients with VHL and is a frequent cause of death. Pheochromocytomas occur in association with specific alleles of the VHL gene; therefore, a family history of pheochromocytoma in association with VHL is an indication for thorough surveillance for pheochromocytoma in affected family members. Recently, it has been appreciated that patients with VHL may develop endolymphatic sac tumors, which can cause tinnitus or deafness. The diagnosis of VHL may be made in a patient with a family history of VHL based on a single retinal or cerebellar hemangioblastoma, renal cell carcinoma or pheochromocytoma, and, possibly, multiple pancreatic cysts. Renal and epididymal cysts are not sufficient to make the diagnosis of VHL. In the absence of a family history of VHL the presence of two or more retinal or cerebellar hemangioblastomas, or one hemangioblastoma with one visceral tumor, is required for diagnosis. Studies of the natural history of VHL showed a life expectancy less than 50 years before surveillance protocols were developed. Annual assessments (physical and ophthalmologic examinations) should begin in infancy. Imaging of abdominal organs and the brain and spine should be added in teenagers and adults. Renal cysts and tumors should be monitored by computed tomography every 6 months. Mutation analysis has allowed presymptomatic identification of affected family members; those found not to have inherited the gene do not need to be monitored. The VHL gene coding sequence contains three exons, and two isoforms of mRNA exist, reflecting the presence or absence of exon 2. Tumors arise after the loss or inactivation of the wild type allele in a cell. About 20% of patients have large germline mutations detectable by Southern blot analysis, 27% have missense mutations, and 27% have nonsense or frameshift mutations. In about 20% of VHL families no deletion or mutation can be detected. Families may be characterized by the presence (type 2; 7% to 20% of families) or absence (type 1) of pheochromocytomas. Most type 2 families have missense mutations, whereas most type 1 families are affected by deletions or premature termination mutations. Prognostic counseling regarding the lifetime risk of pheochromocytoma can be aided by determination of the underlying mutation in patients without family histories of VHL.
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PMID:Von Hippel-Lindau syndrome. A pleomorphic condition. 1063 Jan 73

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that predisposes the affected individual to develop characteristic tumors. These include CNS hemangioblastoma, retinal angiomas, endolymphatic sac tumors, pancreatic cysts and tumors, epididymal cystadenomas, pheochromocytomas, renal cysts, and clear-cell renal carcinoma. The VHL gene was localized to 3p25 and then isolated by Latif et al. (1). The gene contains three exons with an open reading frame of 852 nucleotides, which encode a predicted protein of 284 amino acids. The VHL protein is believed to have several functions. It is involved in transcription regulation through its inhibition of elongation by binding to the B and C subunits of elongin. Mutations of VHL allow the B and C subunits to bind with the A subunit. This complex then overcomes "pausing" of RNA polymerase during mRNA transcription (2,3). Several studies suggest that the VHL protein is also involved in regulation of hypoxia-inducible transcripts, particularly vascular endothelial growth factor (VEGF), by altering mRNA stability (4,5). Therefore, VHL gene mutations permit the overexpression of VEGF under normoxic conditions, which leads to the angiogenesis believed to be required for tumor growth. The VHL-elongin BC complex (VBC) also binds two other proteins-CUL2 and Rbx1-in a complex that has structural similarity to other E3 ubiquitin ligase complexes (6). Such complexes mediate the degradation of cell-cycle regulatory proteins.
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PMID:Molecular analysis of the von hippel-lindau disease gene. 2131 97

Von Hippel-Lindau (VHL) syndrome is a hereditary autosomal dominant disorder caused by defective tumor suppression gene at 3p25-p26. The gene for VHL disease is found on chromosome 3, and is inherited in a dominant fashion. The VHL gene is a tumor suppressor gene. This means that its role in a normal cell is to stop the uncontrolled growth and proliferation. It is characterized by abnormal growth of blood vessels. It strikes the eyes, central nervous system, kidneys, endocrine glands, etc. It predisposes the patient to retinal angiomas, central nervous system hemangioblastoma, renal cell carcinoma (RCC), pheochromocytomas, islet cell tumor of the pancreas, endolymphatic sac tumors, renal, pancreatic, epididymal cysts. We present a case of familial VHL syndrome whose Fluorine 18-fluorodeoxyglucose positron emission tomography-computed tomography scan was truly positive for adrenal pheochromocytoma but was falsely negative for RCC. Review of literature related to this entity is made.
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PMID:Fluorodeoxyglucose positron emission tomography-computed tomography scan in von Hippel-Lindau syndrome: A case report and review of literature. 2372 86