G12S and H50R variations are polymorphisms in the <i>SDHD</i> gene

Cascón, Alberto; Ruiz‐Llorente, Sergio; Cebrián, Arancha; Letón, Rocío; Tellerı́a, Dolores; Benı́tez, Javier; Robledo, Mercedes

doi:10.1002/gcc.10212

Cited by 30 publications

(21 citation statements)

References 9 publications

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“…Since the frequency of the H50R substitution in our series (4% of all patients) is comparable with the frequency that has been reported in the literature for the normal population, we considered it a polymorphism (Perren et al 2002, Cascon et al 2003. The SDHD S68S variant was seen in two patients (one with sPGL and one with bilateral PCC) and has previously been described as a polymorphism (Cascon et al 2004).…”

Section: Discussionsupporting

confidence: 75%

Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma

Korpershoek

Petri²,

Nederveen³

et al. 2007

Endocr Relat Cancer

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Pheochromocytomas (PCCs) are rare tumors that arise from chromaffin tissue in the adrenal medulla, but can also occur in the abdomen outside the adrenals and are then called sympathetic paragangliomas (sPGLs). According to the literature, between 15 and 25% of apparently sporadic adrenal PCC and sPGL are caused by germline mutations in RET, von Hippel-Lindau disease (VHL), succinate dehydrogenase subunit B (SDHB), or subunit D SDHD. However, few studies have addressed the mutation frequency of these candidate genes in selected subgroups of PCC and sPGL, such as bilateral adrenal PCC or extra-adrenal sPGL, and none have looked at somatic mutations by analyzing tumor tissue. Therefore, we have investigated the occurrence of germline and somatic mutations in RET, VHL, SDHB, and SDHD in comparatively large series of bilateral adrenal PCC (nZ 33 patients) and sPGL (nZ26 patients), with the aim of determining the mutation frequency of each of these genes and to establish a genetic testing algorithm. Twenty-one RET, two VHL germline, and one SDHD mutations were found in the patients with bilateral adrenal PCC. In sPGL, one novel SDHB germline and one novel SDHB somatic mutation were observed. In addition, two SDHD germline mutations were found. We conclude that germline RET mutations are predominantly found in bilateral PCC, and that somatic and germline SDHB and SDHD mutations usually occur in sPGL, which has practical consequences for genetic testing algorithms. We suggest that sequential mutation analysis should be directed first at RET, followed by VHL and SDHD for patients with bilateral adrenal PCC at diagnosis, and at SDHB and SDHD for patients with sPGL.

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Section: Discussionsupporting

confidence: 75%

Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma

Korpershoek

Petri²,

Nederveen³

et al. 2007

Endocr Relat Cancer

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“…The prevalence of the G12S in the general population is between 2.5% and 5% (27) according to the Leiden Open Variation Database (http://chromium.liacs.nl) (28), which is somewhat higher than in our control population (1%). This difference may be due to differences in the selection criteria applied for controls.…”

Section: Resultsmentioning

confidence: 51%

Over-representation of the G12S polymorphism of the SDHD gene in patients with MEN2A syndrome

Lendvai¹,

Tóth²,

Valkusz³

et al. 2012

Clinics

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OBJECTIVE:To evaluate whether germline variants of the succinate dehydrogenase genes might be phenotypic modifiers in patients with multiple endocrine neoplasia type 2. Mutations of genes encoding subunits of the succinate dehydrogenase are associated with hereditary paraganglioma/pheochromocytoma syndrome. Pheochromocytoma is one of the main manifestations of multiple endocrine neoplasia type 2 caused by germline mutation of the rearranged during transfection proto-oncogene.METHODS:Polymorphisms of the succinate dehydrogenase genes were analyzed in 77 rearranged during transfection mutation carriers, 47 patients with sporadic medullary thyroid cancer, 48 patients with sporadic Pheo, and 100 healthy individuals. Exons 10–16 of the rearranged during transfection proto-oncogene were analyzed by direct DNA sequencing, and all exons of the von Hippel-Lindau, succinate dehydrogenase B, and succinate dehydrogenase subunit D genes were tested by direct DNA sequencing and multiple ligation probe analysis. The G12S polymorphism of the succinate dehydrogenase subunit D gene was determined by restriction fragment length polymorphism.RESULTS:Of the 77 rearranged during transfection mutation carriers, 55 from 16 families had multiple endocrine neoplasia type 2A, three from three families had multiple endocrine neoplasia type 2B, and 19 from two families had familial medullary thyroid carcinoma. Eight of 55 (14.5%) patients with multiple endocrine neoplasia type 2A had this variant whereas it was absent in multiple endocrine neoplasia type 2B, familial medullary thyroid carcinoma, sporadic medullary thyroid carcinoma, and sporadic pheochromocytoma groups, and its prevalence in controls was 1% (p<0.002 multiple endocrine neoplasia type 2A versus controls). No associations between G12S and age of manifestation, incidence of pheochromocytoma or hyperparathyroidism, or level of serum calcitonin were observed.CONCLUSION:The high prevalence of the G12S variant in patients with multiple endocrine neoplasia type 2A raises questions about its role as a genetic modifier, but this proposal remains to be established.

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“…Given that neither variant had previously been described, we performed a study in a control population; the p.Ser163Pro variant was found in four individuals of the control population tested by SSCP, while the remaining changes were not found in controls. We also detected six polymorphic variants: g.129586_7insCTTCTT in SDHB, 13 p.Gly148Gly, p.Ser68Ser, 5 p.His30His, p.Gly12Ser (19,20) and g.112759GRA in SDHD. 13 Their respective frequencies in the control population are summarised in table 2.…”

Section: Resultsmentioning

confidence: 81%

Genetic and epigenetic profile of sporadic pheochromocytomas

Cascón

2004

Journal of Medical Genetics

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G12S and H50R variations are polymorphisms in the SDHD gene

Cited by 30 publications

References 9 publications

Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma

Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma

Over-representation of the G12S polymorphism of the SDHD gene in patients with MEN2A syndrome

Genetic and epigenetic profile of sporadic pheochromocytomas

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