Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances in the molecular genetic of adrenal tumors give new insights in the pathophysiology of these neoplasms in both hereditary and sporadic cases. The practice of genetic counselling in patients with adrenal tumors have been recently changed by the identification and the understanding of new specific hereditary cancer susceptibility syndromes. In the case of sporadic adrenocortical tumors these progress also offer new prognosis predictors. The genetic predisposition to adrenocortical cancer in children has been well established in the Li-Fraumeni and Beckewith-Wiedeman syndromes due to germline p53 mutation located at 17p13 and dysregulation of the imprinted IGF-2 locus at 11p15, respectively. Adrenocortical tumors are also observed in Multiple Endocrine Neoplasia type I syndrome. Cushing's syndrome due to primary pigmented nodular adrenocortical disease have been observed in patients with germline PRKAR1A inactivating mutations. Interestingly allelic loss at 17p13 and 11p15 have been observed in sporadic adrenocortical cancer and somatic PRKAR1A mutations in secreting adrenocortical adenomas. The potential interest of these finding for the diagnosis of these tumors will be discussed. In the case of pheochromocytoma and paraganglioma, the demonstration that three genes encoding three succinate dehydrogenase subunits (SDHD, SDHB, SDHC), belonging to the complex II of the respiratory chain in the mitochondria, are involved in the genetics of familial and especially in apparently sporadic phaeochromocytomas have dramatically modified our practice. Up to date, four diagnosis of familal disease (multiple endocrine neoplasia type II, von Hippel Lindau disease, neurofibromatosis type 1 and hereditary paraganglioma) should be discussed and causative mutations in six different phaechomocytoma susceptibility genes (RET, VHL, NF1, SDHB, SDHD, SDHC) could be identified. In this review, we will perform an update compiling these new clinical, genetic and functional data recently published. We will suggest guidelines for the practice of the phaeochomocytoma genetic testing in the patients and their families, and for an early detection of tumors in the patients or in individuals determined to be at-risk of disease by the presymptomatic genetic testing.
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PMID:New insights in the genetics of adrenocortical tumors, pheochromocytomas and paragangliomas. 1600 32

There is evidence for a close interrelation between the adrenomedullary and adrenocortical tissues, and there are well-characterized models of their paracrine interaction. To contribute to the studies of systemic interactions between these tissues, we studied a 52-year-old female patient with a pheochromocytoma and a contralateral cortisol-producing adenoma. Due to a misunderstanding, she presented to her family doctor to have an inherited kidney disease ruled out. An adrenal mass was discovered incidentally by ultrasound. A computerized tomography of the abdomen revealed bilateral adrenal masses. Due to excess catecholamine secretion, bilateral pheochromocytomas based on multiple endocrine neoplasia syndrome were suspected. Laboratory work-up, selective adrenal venous sampling and magnetic resonance imaging studies established the diagnosis of a pheochromocytoma in the right-hand adrenal gland and a cortisol-producing adenoma on the left. Simultaneous bilateral laparoscopic subtotal adrenalectomy was performed. Immunohistochemistry showed positive staining against chromogranin A in a histological specimen obtained from the right-hand adrenal gland, while the left was negative; the left-hand adrenal gland stained positive against the ACTH receptor (MC2R) while the right was negative. Genetically, the patient was negative for MEN2, von Hippel-Lindau disease, and mutations in subunits B, C, and D of the succinate dehydrogenase gene. Although presence of bilateral adrenal adenomas or bilateral adrenal pheochromocytomas in certain inherited disorders are possible, this rare case of an adrenal pheochromocytoma combined with a contralateral cortisol-producing adrenal adenoma may further underline the wide range of complex interactions between the two endocrine systems.
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PMID:Adrenal pheochromocytoma with contralateral cortisol-producing adrenal adenoma: diagnostic and therapeutic management. 1600 33

Phaeochromocytomas are rare neuroendocrine tumours with a highly variable clinical presentation but most commonly presenting with episodes of headaches, sweating, palpitations, and hypertension. The serious and potentially lethal cardiovascular complications of these tumours are due to the potent effects of secreted catecholamines. Biochemical testing for phaeochromocytoma is indicated not only in symptomatic patients, but also in patients with adrenal incidentalomas or identified genetic predispositions (eg, multiple endocrine neoplasia type 2, von Hippel-Lindau syndrome, neurofibromatosis type 1, and mutations of the succinate dehydrogenase genes). Imaging techniques such as CT or MRI and functional ligands such as (123)I-MIBG are used to localise biochemically proven tumours. After the use of appropriate preoperative treatment to block the effects of secreted catecholamines, laparoscopic tumour removal is the preferred procedure. If removal of phaeochromocytoma is timely, prognosis is excellent. However, prognosis is poor in patients with metastases, which especially occur in patients with large, extra-adrenal tumours.
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PMID:Phaeochromocytoma. 1611 4

Familial catecholamine secreting tumors have been associated with multiple endocrine neoplasia type 2, Von Hippel-Lindau disease and neurofibromatosis type 1. In the last years, mutations of genes encoding subunits B, C and D of the succinate dehydrogenase have been discovered as other causes of pheochromocytomas and paragangliomas. We diagnosed a malignant retroperitoneal paraganglioma in a 64-yr-old man with bone metastasis in 2001. Two years later a retroperitoneal benign paraganglioma was found and resected in his 32-yr-old daughter. Thus we diagnosed in this family a paraganglioma syndrome. We performed molecular genetic analyses of the genes SDHB, SDHC, and SDHD. We detected in the SDHB gene the mutation SDHB c. 558-3 C> G affecting the splice site of exon 5. In a second daughter the mutation was also detected, thorough clinical investigation revealed normal results. We conclude that the SDHB mutation predisposes to abdominal extra-adrenal and potential malignant pheochromocytoma with incomplete penetrance.
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PMID:The malignant potential of a succinate dehydrogenase subunit B germline mutation. 1669 2

Catecholamine-producing tumours may arise in the adrenal medulla (phaeochromocytomas) or in extra-adrenal chromaffin cells (paragangliomas). The most specific and sensitive diagnostic test is the determination of plasma or urinary metanephrine levels. The tumour can be located by computed tomography, magnetic resonance imaging and metaiodo-benzylguanidine scintigraphy. Patients are treated by tumour resection. Phaeochromocytomas and paragangliomas may be sporadic or the result of several genetic diseases: multiple endocrine neoplasia type 2, neurofibromatosis 1, von Hippel-Lindau disease, succinate dehydrogenase-phaeochromocytoma-paraganglioma syndrome. Familial cases are diagnosed earlier and are more frequently bilateral and recurrent than sporadic cases. About 10% of tumours are malignant, either at initial surgery or during follow-up. Recurrences and malignancy are more frequent in cases with large or extra-adrenal tumours and in the succinate dehydrogenase subunit B-related phaeochromocytoma-paraganglioma syndrome. Patients should be followed up indefinitely, particularly if they have familial or extra-adrenal tumours.
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PMID:Initial work-up and long-term follow-up in patients with phaeochromocytomas and paragangliomas. 1698 Feb 3

Phaeochromocytomas (PC) and paragangliomas are disorders of the sympatho-adrenomedullary system. They are chromaffin-containing neuroendocrine tumors of neural crest origin that contain catecholamine-secreting granules: they arise from either the adrenal medulla (phaeochromocytomas) or from extra-adrenal neural crest derivatives e.g. the sympathetic chain (paragangliomas). The term paraganglioma is also used for vascular head and neck tumors derived from parasympathetic tissue, which commonly arise at the carotid bifurcation. It has been reported that some 10% of phaeochromocytomas are part of a familial syndrome, although recent data have suggested that germline mutations in known predisposing syndromes, such as multiple endocrine neoplasia type 2 (MEN2) and Von Hippel-Lindau (VHL), occur in a much higher percentage. However, familial genetic syndromes have been said to be less common in paragangliomas, although more recently described genetic syndromes may not have been considered. Thus, there is increasing evidence that mutations of subunits of the succinate dehydrogenase gene (SDHB, SDHC & SDHD) may confer susceptibility to paragangliomas and head-and-neck paragangliomas (HNPGL). We report a case of a patient with a previously published gene mutation in SDHB who had a single paraganglioma arising from the bladder with a characteristic clinical presentation, and in whom there was a positive family history of a HNPGL. He has demonstrated malignant recurrence with metastases which have been treated, so far successfully, with radiolabelled MIBG.
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PMID:Familial paraganglioma: a novel presentation of a case and response to therapy with radiolabelled MIBG. 1698 87

Hereditary pheochromocytomas and paragangliomas are caused by germline mutations in syndrome-associated genes. This includes multiple endocrine neoplasia Type 2 (MEN 2) caused by mutations in the RET proto-oncogene, von Hippel-Lindau (VHL) syndrome due to mutations of the VHL gene, neurofibromatosis Type I (NF1) caused by mutations of the NF1 gene, and pheochromocytoma/paraganglioma syndromes due to mutations in genes encoding the succinate dehydrogenase subunits D (SDHD) and B (SDHB). At the First International Symposium on Pheochromocytoma (ISP2005) organized by the National Institutes of Health, a panel of specialist clinicians and scientists from around the world addressed the topic of genetic testing in pheochromocytoma patients. This review summarizes the discussions and conclusions of the panel and provides a recommendation for evidence-based management of genetic testing in these patients and their families. A pragmatic algorithm is presented, taking into account patient age, tumor location (extra-adrenal, intra-adrenal, unilateral, and bilateral), biochemical presentation, and financial costs. This was based on cumulative frequencies ranging from 7.5% to 29% for germline mutations in four genes (RET, VHL, SDHB, and SDHD) in patients with apparently sporadic pheochromocytomas. This algorithm will need to be validated by further genetic analysis, multicenter studies, and long-term observations.
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PMID:Genetic testing in pheochromocytoma: increasing importance for clinical decision making. 1710 76

Mutations in the genes encoding succinate dehydrogenase (SDH) have been associated with susceptibility to pheochromocytoma. However, few reports have examined the level of SDH mRNAs expression. In this study, we examined the level of expression of mRNAs encoding SDHB, SDHC, and SDHD in pheochromocytoma, pheochromocytoma subgroups, and normal adrenal gland, and compared the expression of these genes to the level of expression of related genes in the same tissues. The mean relative level of expression of SDHB, SDHC, SDHD and VHL mRNA was 28.7+/-6.2%, 16.6+/-4.8%, 214+/-47.5% and 25.9+/-8.2%, respectively, in pheochromocytoma tissues compared to normal adrenal gland. Furthermore, the mean relative level of the RET proto-oncogene mRNA was 707+/-149% in pheochromocytoma compared to normal adrenal gland. The level of expression of the SDH genes was highly correlated in each individual sample (P<0.0001). The level of expression of the SDH mRNAs correlated with the level of VHL mRNA (P<0.0001), but not with the level of RET mRNA. The level of SDH mRNAs expression also correlated with the expression of phenylethanolamine N-methyl transferase (PNMT), an adrenaline synthesizing enzyme (P<0.01), which may explain the correlation between SDH expression and adrenaline content (P<0.05). The level of SDH mRNAs expression correlated strongly with the expression of VEGF mRNA (P<0.0001). In multiple endocrine neoplasia (MEN) 2a, the expression of the SDH genes and VHL mRNA was significantly higher than that observed in adrenal or extra-adrenal pheochromocytoma. The expression of the corticotropin-releasing hormone (CRH) mRNA was significantly higher in extra-adrenal pheochromocytoma than in adrenal pheochromocytoma or MEN2a. Thus, tumor-specific gene expression exists in pheochromocytoma, which may explain the characteristics of the tumor.
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PMID:Expression of mRNAs for succinate dehydrogenase subunits and related genes in pheochromocytoma. 1710 93

Pheochromocytoma (PHEO) is considered to be a rare cause of hypertension. However, if left untreated, PHEOs may lead to fatal hypertensive crises during anesthesia and other stresses. The diagnosis of PHEO is therefore extremely important. A 24-hour blood pressure (BP) pattern per se might be of some diagnostic value due to frequently observed higher BP variability as well as an attenuated night-time BP decrease. So far, germline mutations in five genes have been identified to be responsible for familial PHEOs: the von Hippel-Lindau gene, which causes von Hippel-Lindau syndrome, the RET gene leading to multiple endocrine neoplasia type 2, the neurofibromatosis type 1 gene, which is associated with von Recklinghausen's disease and the genes encoding the B and D subunits of mitochondrial succinate dehydrogenase (SDHB, SDHD), which are associated with familial paragangliomas and PHEOs. Genetic analysis should be offered to those patients with confirmed PHEO who are 50 years old or younger. Plasma-free metanephrines or urinary fractionated metanephrines seem to have higher diagnostic values compared to plasma or urinary catecholamines for the biochemical diagnosis of PHEO. Imaging with (123)I-metaiodobenzylguanidine or (18)F-fluorodopamine PET, if available, are in addition to CT/MRI useful for the detection of multifocal/extra-adrenal forms. Appropriate pharmacologic treatment with subsequent laparoscopic extirpation of PHEO is usually successful in benign forms. There is, however, no convincingly effective mode of treatment in malignant PHEOs.
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PMID:Recent advances in the diagnosis and treatment of pheochromocytoma. 1711 41

Pheochromocytomas and paragangliomas are rare tumors derived from chromaffin cells. These tumors can arise in the context of hereditary cancer syndromes such as von Hippel- Lindau disease, multiple endocrine neoplasia type 2, and neurofibromatosis 1. Recent studies indicate that germ line mutations of genes encoding specific succinate dehydrogenase (SDH) subunits also predispose individuals to pheochromocytomas and paragangliomas. This review focuses on the genetics of these tumors and suggests a possible link between familial pheochromocytomas/paraganglioma genes and control of neuronal apoptosis during embryological development.
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PMID:Recent insights into the molecular pathogenesis of pheochromocytoma and paraganglioma. 1715 41


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