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)

Pheochromocytoma and paraganglioma (PGL) are rare neuroendocrine tumors in children. Apparently sporadic cases of PGL may harbor germline mutations in the succinate dehydrogenase (SDHx) gene. SDHB mutations are associated with malignant disease. We report a 13-year-old African American boy with diffusely metastatic PGL and compound heterozygous mutation leading to a novel splice donor region DNA sequence variant in the SDHB gene. Family history was positive for non-classical congenital adrenal hyperplasia and pituitary adenoma. After surgical resection of the primary PGL and chemotherapy, he was treated with metaiodobenzy lguanidine (MIBG) combined with arsenic trioxide. At 3-year follow-up, he had stable disease.
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PMID:Compound heterozygous mutation with a novel splice donor region DNA sequence variant in the succinate dehydrogenase subunit B gene in malignant paraganglioma. 2021 50

Mutations in the subunits B, C, D, and recently in A of the succinate dehydrogenase have been associated with the development of paragangliomas. We report the case of a 37-year-old man presented with multiple paragangliomas and a growth hormone-producing pituitary adenoma, with a novel succinate dehydrogenase subunit D mutation as the genetic analysis revealed. We present the similarities and the differences of the findings in patient imaging with either methods of SPECT (I-MIBG and In-pentetreotide) or PET/CT with F-FDG. This case revealed that F-FDG PET/CT detected more lesions and was superior compared with the other methods.
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PMID:SPECT and 18F-FDG PET/CT imaging of multiple paragangliomas and a growth hormone-producing pituitary adenoma as phenotypes from a novel succinate dehydrogenase subunit D mutation. 2415 17

The tricarboxylic acid, or Krebs, cycle is central to the cellular metabolism of sugars, lipids, and amino acids; it fuels the mitochondrial respiratory chain for energy generation. In the past decade, mutations in the Krebs-cycle enzymes succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase have been documented to be causally involved in carcinogenesis. This review is focused on the relationship between SDH mutations and the carcinogenic phenotype. The succinate dehydrogenase complex catalyzes the oxidation of succinate to fumarate; mutations in its subunits SDHA, SDHB, SDHC, and SDHD, and in the assembly factor SDHAF2, result in syndromes with distinct tumor types, including pheochromocytoma/paraganglioma, gastrointestinal stromal tumor, and, less often, renal-cell carcinoma and pituitary adenoma. In this study we collected all previously reported SDH mutations with the aim of defining their nature and tumor spectrum. In addition, genotype-phenotype correlations as well as mechanisms of biallelic inactivation were analyzed in the SDH-deficient setting. Finally, we performed bioinformatics analysis using SIFT, Polyphen2, and Mutation Assessor to predict the functional impact of nonsynonymous mutations. The prediction of the latter was further compared with available SDHA and/or SDHB immunohistochemistry data.
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PMID:Toward an improved definition of the genetic and tumor spectrum associated with SDH germ-line mutations. 2539 76

Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly.
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PMID:Genetics of gigantism and acromegaly. 2765 86

Symptomatic pituitary adenomas occur with a prevalence of approximately 0.1% in the general population. It is estimated that 5% of pituitary adenomas occur in a familial setting, either in isolated or syndromic form. Recently, loss-of-function mutations in genes encoding succinate dehydrogenase subunits (SDHx) or MYC-associated factor X (MAX) have been found to predispose to pituitary adenomas in co-existence with paragangliomas or phaeochromocytomas. It is rare, however, for a familial SDHx mutation to manifest as an isolated pituitary adenoma. We present the case of a pituitary lactotroph adenoma in a patient with a heterozygous germline SDHB mutation, in the absence of concomitant neoplasms. Initially, the adenoma showed biochemical response but poor tumour shrinkage in response to cabergoline; therefore, transsphenoidal surgery was performed. Following initial clinical improvement, tumour recurrence was identified 15 months later. Interestingly, re-initiation of cabergoline proved successful and the lesion demonstrated both biochemical response and tumour shrinkage. Our patient's SDHB mutation was identified when we realised that her father had a metastatic paraganglioma, prompting genetic testing. Re-inspection of the histopathological report of the prolactinoma confirmed cells with vacuolated cytoplasm. This histological feature is suggestive of an SDHx mutation and should prompt further screening for mutations by immunohistochemistry and/or genetic testing. Surprisingly, immunohistochemistry of this pituitary adenoma demonstrated normal SDHB expression, despite loss of SDHB expression in the patient's father's paraganglioma.
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PMID:A patient with a germline SDHB mutation presenting with an isolated pituitary macroprolactinoma. 3008 76

Pituitary adenomas in children and adolescents are rare tumors that often result from a tumor predisposition syndrome. Several inherited causes for pituitary adenomas have been identified in the last few years, including multiple endocrine neoplasia type 1 and 4, Carney's complex, Tuberous sclerosis, DICER1 syndrome, neurofibromatosis type 1, McCune Albright syndrome, familial isolated pituitary adenoma, and pituitary adenoma association due to defects in succinate dehydrogenase genes. Recently, our group discovered X-linked acrogigantism (X-LAG), a new pediatric disorder that is caused by an Xq26.3 genomic duplication (involving the GPR101 gene). Genes that predispose to pediatric Cushing disease, including CABLES1 and USP8, were also recently identified. Genetic screening and counseling of affected or at risk individuals is a key component of their comprehensive care. In this review, we provide an up-to-date discussion on the latest pediatric genetic discoveries associated with pituitary adenomas with a focus on familial syndromes.
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PMID:An update on the genetics of benign pituitary adenomas in children and adolescents. 3055 57

Pituitary adenomas are frequently occurring neoplasms that produce clinically significant disease in 1:1000 of the general population. The pathogenesis of pituitary tumors is a matter of interest as it could help to improve diagnosis and treatment. Until recently, however, disruptions in relatively few genes were known to predispose to pituitary tumor formation. In the last decade, several more genes and pathways have been described. Germline pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene were found in familial or sporadic pituitary adenomas, usually with an aggressive clinical course. Cyclin-dependent kinase inhibitor 1B (CDKN1B) pathogenic variants lead to multiple endocrine neoplasia type 4 (MEN4) syndrome, in which pituitary adenomas can occur. Xq26.3 duplications involving the gene GPR101 cause X-linked acrogigantism. The pheochomocytoma and/or paraganglioma with pituitary adenoma association (3PAs) syndrome suggests that pathogenic variants in the genes of the succinate dehydrogenase complex or MYC-associated factor X (MAX) might be involved in pituitary tumorigenesis. New recurrent somatic alterations were also discovered in pituitary adenomas, such as, ubiquitin-specific protease 8 (USP8) and USP48 pathogenic variants in corticotropinomas. The aim of the present review is to provide an overview of the genetic pathophysiology of pituitary adenomas and their clinical relevance.
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PMID:Somatic and germline mutations in the pathogenesis of pituitary adenomas. 3165 40