Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.

  title={Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.},
  author={Dewi Astuti and Farida Latif and Ashraf Dallol and Patricia L. M. Dahia and F. Easton Douglas and Emad George and F Sk{\"o}ldberg and Eystein Sverre Husebye and Charis Eng and Eamonn R. Maher},
  journal={American journal of human genetics},
  volume={69 1},
The pheochromocytomas are an important cause of secondary hypertension. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of nonsyndromic familial pheochromocytoma is unknown. Recently, pheochromocytoma susceptibility has been associated with germline SDHD mutations. Germline SDHD mutations were originally described in hereditary paraganglioma, a dominantly… 

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Novel Germline Mutations in the SDHB and SDHD Genes in Japanese Pheochromocytomas

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Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas

SDHB has a major role in the pathogenesis of familial phaeochromocytomas, but the possible role of SDHB in sporadic tumours showing allelic loss at 1p36 has yet to be ascertained.

Large germline deletions of mitochondrial complex II subunits SDHB and SDHD in hereditary paraganglioma.

More than 30% of adrenal pheochromocytomas are hereditary. These neuroendocrine tumors are major components of three inherited cancer syndromes: multiple endocrine neoplasia type 2, von Hippel-Lindau

No mutations but an increased frequency of SDHx polymorphisms in patients with sporadic and familial medullary thyroid carcinoma.

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Mutation Analysis of the SDHD Gene in Four Kindreds with Familial Paraganglioma: Description of One Novel Germline Mutation

Genetic testing of SDHD may be a powerful tool for the identification of the syndrome in patients with multiple or bilateral paragangliomas, as well as in several asymptomatic carriers.

Mutation analysis of the SDHB and SDHD genes in pheochromocytomas and paragangliomas: identification of a novel nonsense mutation (Q168X) in the SDHB gene.

A novel heterozygous nonsense mutation at codon 168 resulting in a CAG (glutamine) to TAG (stop) substitution (Q168X) in the SDHB gene in a patient diagnosed with solitary sporadic PGL is identified.

SDHB, SDHC, and SDHD mutation screen in sporadic and familial head and neck paragangliomas

The presence of mutations within SDHB and SDHD in two of the three samples of familial PGLs and absence of mutations in sporadic cases is consistent with the significant contribution of these genes to familial but not sporadic PGL.

Yeast model for evaluating the pathogenic significance of SDHB, SDHC and SDHD mutations in PHEO-PGL syndrome.

The results of this study demonstrate that the yeast is a good functional model to validate the pathogenic significance of SDHB missense mutations while, for missesense mutations in SDHC and SDHD genes, the model can be informative only when the variation involves a conserved residue in a Conserved domain.

Identification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma

Two previously unreported mutations in two patients from 25 unrelated kindreds with phaeochromocytoma and/or paraganglioma disorders and with or without familial antecedents are described: a mutation featuring the change of tryptophan to a termination codon in exon 2, and a 4-bp deletion inExon 4 that results in a truncated protein.



Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL1), in pheochromocytomas.

In conclusion, mutations of the SDHD gene are not a common event in this series of sporadic pheochromocytomas, and the existence of SDHD pseudogenes should be considered when analyzing complementary DNA-based samples.

Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma.

The results indicate that SDHD plays a role in the pathogenesis of pheochromocytoma and suggests that all patients with hereditary paraganglioma should be considered for SDHD mutation analysis.

Germline SDHD mutation in familial phaeochromocytoma

Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.

Analysis of families carrying the PGL1 gene revealed germ line mutations in the SDHD gene, which indicates that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology.

Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome

Deep deficiencies in complex II activity resulting from mutations in the Fp gene of the SDH present only as LS are reported, a striking observation in view of the ubiquitous expression of this typical housekeeping gene in humans.

Genetic predisposition to phaeochromocytoma: analysis of candidate genes GDNF, RET and VHL.

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Molecular genetic diagnosis of von Hippel-Lindau disease in familial phaeochromocytoma.

Patients with familial, multiple, or early onset phaeochromocytoma should be investigated for germline VHL and RET gene mutations as the molecular diagnosis of multisystem familial cancer syndromes enables appropriate counselling and screening to be provided.

Sporadic and familial pheochromocytomas are associated with loss of at least two discrete intervals on chromosome 1p.

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Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency

A mutation in the nuclear–encoded flavoprotein (Fp) subunit gene of the succinate dehydrogenase (SDH) is reported in two siblings with complex II deficiency presenting as Leigh syndrome, the first report of a nuclear gene mutation causing a mitochondrial respiratory chain deficiency in humans.

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