Genetics of Pheochromocytoma and Paraganglioma in Spanish Patients

Cascón, Alberto; Pita, Guillermo; Burnichon, Nelly; Landa, Iñigo; López‐Jiménez, Elena; Montero‐Conde, Cristina; Leskelä, Susanna; Leandro‐García, Luis Javier; Letón, Rocío; Rodríguez‐Antona, Cristina; Díaz, José Ángel; López-Vidriero, Emilio; González‐Neira, Anna; Velasco, Ana; Matías‐Guiu, Xavier; Gimenez-Roqueplo, Anne-Paule; Robledo, Mercedes

doi:10.1210/jc.2008-2756

Cited by 115 publications

(137 citation statements)

References 16 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…It is also thought that 4-25% of seemingly sporadic CNS hemangioblastomas are due to VHL germline mutations, and thus some have recommended VHL genetic screening for patients presenting with such lesions [Fukino et al, 2000;Hes et al, 2000;Neumann et al, 1989]. As many as 25% of patients with seemingly sporadic pheochromocytomas (without family history) actually have a germline mutation in genes responsible for hereditary syndromes, such as VHL, c-RET, NF1, SDHB, or SDHD (SDHD, SDHB) [Astuti et al, 2001;Cascó n et al, 2009;Neumann et al, 2002]; thus, germline mutation screening is often recommended for these cases as well [Cascó n et al, 2009;Neumann et al, 2002].…”

Section: Diagnosismentioning

confidence: 99%

“…Untreated pheochromocytomas can result in hypertension and subsequent acute heart disease, brain edema, and stroke. Familial pheochromocytomas are often a result of mutations in VHL (MIM]s 193300, 608537), Neurofibromatosis-1 (NF1), c-RET (mutated in Multiple Endocrine Neoplasia-2), or succinate dehydrogenase (SDHB, SDHC, SDHD) genes [Astuti et al, 2001;Cascó n et al, 2009;Lee et al, 2005;Neumann et al, 2002;Pacak, 2007]. However, true sporadic pheochromocytomas rarely have somatic mutations in these genes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic analysis of von Hippel-Lindau disease

et al. 2010

View full text Add to dashboard Cite

Mutations in the von Hippel-Lindau (VHL) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types as well. Reports of VHL mutations are dispersed throughout original articles and databases that have not been recently updated. We compiled a comprehensive mutation table of 1,548 germline and somatic VHL mutations, derived from this protein of only 213 amino acids. We describe detailed phenotype and gene mutation information for 945 VHL families, including 30 previously unpublished kindreds from The Netherlands (six novel mutations). These data represent the most extensive catalog of germline VHL mutations to date. We also review VHL disease, known and theorized pathogenesis of common VHL manifestations, and genotype-phenotype correlations. Analysis of all VHL families, excluding germline mutations resulting in congenital polycythemias, describes the spectrum of mutation types: 52% missense, 13% frameshift, 11% nonsense, 6% in-frame deletions/insertions, 11% large/complete deletions, and 7% splice mutations. This easy-to-use compilation of VHL mutations is intended to facilitate research and function as a necessary adjunct for physicians when providing patient information. Hum Mutat 31:521-537,

show abstract

Section: Diagnosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic analysis of von Hippel-Lindau disease

et al. 2010

View full text Add to dashboard Cite

show abstract

“…In a large cohort of Spanish patients, seven independent families were found to carry deletion in the SDHB gene, representing 28% of positive SDHB cases [17]. the presence of founder mutations in the Spanish population could also explain the high rate of SDHB mutations in this series.…”

Section: Discussionmentioning

confidence: 73%

“…while the majority of patients undergoing SDHB mutation analysis have missense and nonsense mutations, some mutation negative patients have been reported to carry either large partial or total deletions of the SDHB gene [10][11][12][13][14][15][16][17][18]. to investigate this possibility, we carried out MLPA and identified a heterozygous SDHB gene deletion encompassing sequences corresponding to the promoter region, exon 1 and exon 2 ( Fig.…”

Section: Sdhb Mutation Analysismentioning

confidence: 99%

“…Since large deletions are rare and are undetectable using this method, neither the frequency nor the clinical manifestation associated with large SDHB deletions is well known. recently, in addition to these mutations, the use of methods such as multiplex ligation-dependent probe amplification (MLPA) and quantitative multiplex PCR of short fluorescent fragments (QmPSF) have resulted in increased reports of large SDHB deletions [10][11][12][13][14][15][16][17][18].…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Large Deletion in the Succinate Dehydrogenase B Gene (SDHB) in a Japanese Patient with Abdominal Paraganglioma and Concomitant Metastasis

et al. 2010

View full text Add to dashboard Cite

The nuclear genes encoding two mitochondrial complex II subunit proteins, succinate dehydrogenase D (SDHD) and SDHB, have been reported to be associated with the development of familial pheochromocytoma and paraganglioma (hereditary pheochromocytoma/paraganglioma syndrome: HPPS) [1,2]. Growing evidence suggests that point mutations in SDHB are highly associated with abdominal paraganglioma and the following distant metastasis (malignant paraganglioma) [3][4][5][6][7][8]. Indeed, it has been found that SDHB mutations are present in 40% to 50% of malignant pheochromocytoma/paraganglioma patients which far exceeds the incidence of mutations of other genes in these malignant tumors. By contrast, among all patients with malignant pheochromocytoma/paraganglioma, the frequency of SDHB mutations is re- . Growing evidence suggests that the mutation of SDHB is highly associated with abdominal paraganglioma and the following distant metastasis (malignant paraganglioma). In the present study, we used multiplex ligation dependent probe amplification (MLPA) analysis to identify a large heterozygous SDHB gene deletion encompassing sequences corresponding to the promoter region, in addition to exon 1 and exon 2, in a malignant paraganglioma patient in whom previously characterized SDHB mutations were undetectable. This is the first Japanese case report of malignant paraganglioma, with a large SDHB deletion. our present findings strongly support the notion that large deletions in the SDHB gene should be considered in patients lacking characterized SDHB mutations.Key words: malignant pheochromocytoma, SDHB, MLPA, HPPS (hereditary pheochromocytoma/paraganglioma syndrome), Paraganglioma ported to be around one third, suggesting that SDHB mutations in these malignant tumors may not be as rare as expected [9]. It should be noted, however, that these findings are based on mutations including point mutations as well as small deletions, which are detectable by direct sequencing method [3][4][5][6][7][8][9]. Since large deletions are rare and are undetectable using this method, neither the frequency nor the clinical manifestation associated with large SDHB deletions is well known. recently, in addition to these mutations, the use of methods such as multiplex ligation-dependent probe amplification (MLPA) and quantitative multiplex PCR of short fluorescent fragments (QmPSF) have resulted in increased reports of large SDHB deletions [10][11][12][13][14][15][16][17][18].Here we report a large heterozygous SDHB gene deletion encompassing sequences corresponding to the promoter region, in addition to exon 1 and exon 2, in a malignant paraganglioma patient in whom previously characterized SDHB mutations were undetectable. This is the first Japanese case report of malignant

show abstract

Spectrum and Prevalence of FP/TMEM127 Gene Mutations in Pheochromocytomas and Paragangliomas

Yao¹,

Schiavi²,

Cascón³

et al. 2010

JAMA

Self Cite

184

159

View full text Add to dashboard Cite

HEOCHROMOCYTOMAS AND paragangliomas are chromaffin cell tumors of neural crest origin that arise from the adrenal medulla or extra-adrenal sympathetic paraganglia, respectively, and are frequently catecholamine secreting. 1 These tumors are usually benign and can occur as a single entity or as part of various hereditary tumor syndromes. Genetically, pheochromocytomas and paragangliomas are heterogeneous , with at least one-third of cases resulting from germline but not somatic mutations in 1 of several independent genes: RET, VHL, NF1, and succinate dehydrogenase (SDH) subunit B, C, and D genes. 2-5 More recently, other candidate susceptibil-Author Affiliations are listed at the end of this article.

show abstract

Genetics of Pheochromocytoma and Paraganglioma in Spanish Patients

Cited by 115 publications

References 16 publications

Genetic analysis of von Hippel-Lindau disease

Genetic analysis of von Hippel-Lindau disease

A Large Deletion in the Succinate Dehydrogenase B Gene (SDHB) in a Japanese Patient with Abdominal Paraganglioma and Concomitant Metastasis

Spectrum and Prevalence of FP/TMEM127 Gene Mutations in Pheochromocytomas and Paragangliomas

Contact Info

Product

Resources

About