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Zantour B Guilhaume B Tissier F Louvel A Jeunemaitre X Gimenez-Roqueplo AP Bertagna X 《European journal of endocrinology / European Federation of Endocrine Societies》2004,151(4):433-438
A 32-year-old asymptomatic female was diagnosed with an isolated thyroid nodule of 2.5 cm diameter. Fine needle aspiration suggested a medullary thyroid carcinoma. Consequently, a total thyroidectomy was performed. The nodule stained positive for chromogranin A, neurone-specific enolase and synaptophysin, but not for calcitonin. Finally, pathological analysis showed a thyroid paraganglioma. Although the tumour appeared to be sporadic in a patient with no personal or familial history of paraganglioma and/or pheochromocytoma, we have identified a new mutation (392delC) of the succinate dehydrogenase-B (SDHB) gene in the genomic DNA extracted from the leukocytes of the patient. That mutation induced a shift in the reading frame of the gene creating a premature stop codon (P131fsX135) which was predicted to result in a truncated SDHB protein of 135 amino acids.This report highlights the difficulties of this unexpected diagnosis of hereditary thyroid paraganglioma. It also discusses the clinical involvements in terms of familial screening and the necessary follow-up of the patient. 相似文献
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Plouin PF Gimenez-Roqueplo AP La Batide Alanore A Salenave S Duclos JM 《La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne》2000,21(12):1075-1085
INTRODUCTION: Pheochromocytoma is a catecholamine-secreting neoplasm of chromaffin tissue. It is a rare disease. Biochemical tests should be performed only in patients at high risk of pheochromocytoma, and an imaging procedure only in those with positive biochemical tests. CURRENT KNOWLEDGE AND KEY POINTS: The most specific and sensitive diagnostic test for the disease is the determination of plasma or urinary metanephrines. The tumor can be located by computerized tomography, magnetic resonance imaging, and specific scintigraphy. Ten to 20% of pheochromocytomas result from hereditary diseases, including multiple endocrine neoplasia type 2, von Hippel Lindau disease, and neurofibromatosis 1. Familial cases are diagnosed earlier, and are more frequently bilateral and recurring than sporadic cases. About 10% of the cases are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. The probability of a recurrence is positively correlated with the urinary excretion of metanephrines and tumor size. Recurrences are more frequent in cases with ectopic tumors and in those with a low plasma epinephrine to total catecholamine ratio. Patients, especially those with familial tumors or low epinephrine secretion, should be followed-up indefinitely. FUTURE PROSPECTS AND PROJECTS: Treatment for malignant recurrences includes surgery, therapeutic embolization, chemotherapy, and the application of therapeutic doses of metaiodobenzylguanidine. Metyrosine, phenoxybenzamine, or somatostatin analogs may help to control blood pressure and to alleviate symptoms in patients with malignant pheochromocytoma; however such a treatment has no antiproliferative effect. 相似文献
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Mitochondrial succinate is instrumental for HIF1alpha nuclear translocation in SDHA-mutant fibroblasts under normoxic conditions 总被引:2,自引:0,他引:2
Brière JJ Favier J Bénit P El Ghouzzi V Lorenzato A Rabier D Di Renzo MF Gimenez-Roqueplo AP Rustin P 《Human molecular genetics》2005,14(21):3263-3269
The genes encoding succinate dehydrogenase (SDH) subunits B, C and D, act as tumour suppressors in neuro-endocrine tissues. Tumour formation has been associated with succinate accumulation. In paraganglioma cells, two forms of SDHA (type I, II) were found which might preclude significant succinate accumulation in the case of a mutation in either form. In fibroblasts only SDHA type I is found. In these cells, SDHA type I mutation leads to SDH deficiency, succinate accumulation and hypoxia-inducible factor 1alpha(HIF1alpha) nuclear translocation. HIF1alpha nuclear translocation was not observed in ATPase-deficient fibroblasts with increased superoxide production and was found to be independent of cellular iron availability in SDHA-mutant cells. This suggests that neither superoxides nor iron were causative of HIF1alpha nuclear translocation. Conversely, alpha-ketoglutarate (alpha-KG) inhibits this nuclear translocation. Therefore, the pseudo-hypoxia pathway in SDH-deficient cells depends on the HIF1alphaprolyl hydroxylase product/substrate (succinate/alpha-KG) equilibrium. In SDH deficiency, organic acids thus appear instrumental in the HIF1alpha-dependent cascade suggesting a direct link between SDH and tumourigenesis. 相似文献
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Daly AF Vanbellinghen JF Khoo SK Jaffrain-Rea ML Naves LA Guitelman MA Murat A Emy P Gimenez-Roqueplo AP Tamburrano G Raverot G Barlier A De Herder W Penfornis A Ciccarelli E Estour B Lecomte P Gatta B Chabre O Sabaté MI Bertagna X Garcia Basavilbaso N Stalldecker G Colao A Ferolla P Wémeau JL Caron P Sadoul JL Oneto A Archambeaud F Calender A Sinilnikova O Montañana CF Cavagnini F Hana V Solano A Delettieres D Luccio-Camelo DC Basso A Rohmer V Brue T Bours V Teh BT Beckers A 《The Journal of clinical endocrinology and metabolism》2007,92(5):1891-1896
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Perdu J Boutouyrie P Bourgain C Stern N Laloux B Bozec E Azizi M Bonaiti-Pellié C Plouin PF Laurent S Gimenez-Roqueplo AP Jeunemaitre X 《Journal of human hypertension》2007,21(5):393-400
We have previously shown that patients with renal fibromuscular dysplasia (FMD) have asymptomatic carotid lesions and that familial forms may occur. The objective of this study was to test whether carotid lesions could be detected in relatives of familial cases. High-resolution echotracking of the carotid artery was performed in 47 relatives of 13 cases from six families. This non-invasive investigation led to a semiquantitative arterial score that was compared with that obtained for 47 controls matched for age and sex and that for 125 sporadic cases. Familial resemblance was tested by using a generalized estimating equation approach taking into account the clustering of scores in families. As expected, FMD cases had a significantly higher score than controls (4.02 vs 2.52, P<10(-5)). Familial cases were not significantly different from sporadic cases. Of interest, the 47 apparently healthy relatives of familial cases had also a high carotid score (4.17), very significantly higher than that of controls (2.52, P<10(-5)) even though lower than the corresponding index FMD cases (4.81, P=0.01). Segregation analysis showed that 52% of the descendants of subjects with a score >4 had a score >4, a proportion consistent with autosomal-dominant transmission of the trait. Altogether these results strengthen the hypothesis of renal FMD being a systemic arterial disease and argue for a familial resemblance that may be due to a major genetic effect. The carotid score obtained by high-resolution echotracking may provide a non-invasive surrogate marker for renal FMD of potential value for use in linkage strategies on large pedigrees. 相似文献
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Bonnet S Durand X Baton O Gimenez-Roqueplo AP Baudin E Visset J Algayres JP Baranger B 《Annales de chirurgie》2006,131(10):626-630
Non-functional paraganglioma have not clinical or biological characteristics, so that the diagnostic is most of the time delayed and made on the occasion of advanced abdominal tumor or symptomatic metastasis management. Hereditary forms, notably those with SDHB mutation, seem to have a poor prognosis. On the other hand, and on the oposite to sporadic forms, they are the only ones to benefit from genetic testing which make possible, if positive, an earlier diagnostic, before apparition of symptoms, recurrence or metastasis. We report a case of non-functional malignant hereditary paraganglioma diagnosed belatedly and we will consider management problems raised by non-functional forms. 相似文献
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Vargas-Poussou R Dahan K Kahila D Venisse A Riveira-Munoz E Debaix H Grisart B Bridoux F Unwin R Moulin B Haymann JP Vantyghem MC Rigothier C Dussol B Godin M Nivet H Dubourg L Tack I Gimenez-Roqueplo AP Houillier P Blanchard A Devuyst O Jeunemaitre X 《Journal of the American Society of Nephrology : JASN》2011,22(4):693-703
Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene. 相似文献
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Pasini B McWhinney SR Bei T Matyakhina L Stergiopoulos S Muchow M Boikos SA Ferrando B Pacak K Assie G Baudin E Chompret A Ellison JW Briere JJ Rustin P Gimenez-Roqueplo AP Eng C Carney JA Stratakis CA 《European journal of human genetics : EJHG》2008,16(1):79-88
Gastrointestinal stromal tumors (GISTs) may be caused by germline mutations of the KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes and treated by Imatinib mesylate (STI571) or other protein tyrosine kinase inhibitors. However, not all GISTs harbor these genetic defects and several do not respond to STI571 suggesting that other molecular mechanisms may be implicated in GIST pathogenesis. In a subset of patients with GISTs, the lesions are associated with paragangliomas; the condition is familial and transmitted as an autosomal-dominant trait. We investigated 11 patients with the dyad of 'paraganglioma and gastric stromal sarcoma'; in eight (from seven unrelated families), the GISTs were caused by germline mutations of the genes encoding subunits B, C, or D (the SDHB, SDHC and SDHD genes, respectively). In this report, we present the molecular effects of these mutations on these genes and the clinical information on the patients. We conclude that succinate dehydrogenase deficiency may be the cause of a subgroup of GISTs and this offers a therapeutic target for GISTs that may not respond to STI571 and its analogs. 相似文献