TY - JOUR
T1 - Genetic-clinical profile of subjects with apparently sporadic extra-adrenal paragangliomas
AU - Ramundo, Valeria
AU - Ercolino, Tonino
AU - Faggiano, Antongiulio
AU - Giachè, Valentino
AU - Ragghianti, Benedetta
AU - Rapizzi, Elena
AU - Colao, Annamaria
AU - Mannelli, Massimo
PY - 2012
Y1 - 2012
N2 - Background: Mutations in the genes encoding B, C, and D subunits of the succinate dehydrogenase (SDH) are involved in the pathogenesis of familial paraganglioma (PGL) syndrome. Many subjects with apparently sporadic extra-adrenal paragangliomas are found to be carrier for SDH mutation. Objective: Here we describe four subjects with apparently sporadic extra-adrenal paragangliomas with newly identified mutations in the SDH subunit B and the related clinical phenotype. Methods: Gene sequencing was performed to search for mutations in the SDHB (all exons), SDHC (all exons), and SDHD (all exons) genes as well as VHL (all exons) and RET (10, 11, 13, 14, 15, 16 exons) genes in all four index cases. A complete clinical, biochemical, and instrumental work-up was performed. Results:Three subjects were found to be affected with a nonsense SDHB germline mutation (Q30X, Y61X, and W201X, respectively). These mutations are predicted to encode for a truncated SDHB protein. The fourth subject presented a S195del frameshift mutation, causing a deletion of the codon AGC, encoding for a serine. Clinical presentation and course of each patient is described. Conclusions: Extra-adrenal paragangliomas, localized in the sympathetic ganglia (in the posterior thorax or in the abdomen), are very often SDHB-inherited form rather than sporadic tumor. Our data confirm the importance of genetic screening in patients affected with paragangliomas and enlarge the list of mutations responsible for the presence of these tumors.
AB - Background: Mutations in the genes encoding B, C, and D subunits of the succinate dehydrogenase (SDH) are involved in the pathogenesis of familial paraganglioma (PGL) syndrome. Many subjects with apparently sporadic extra-adrenal paragangliomas are found to be carrier for SDH mutation. Objective: Here we describe four subjects with apparently sporadic extra-adrenal paragangliomas with newly identified mutations in the SDH subunit B and the related clinical phenotype. Methods: Gene sequencing was performed to search for mutations in the SDHB (all exons), SDHC (all exons), and SDHD (all exons) genes as well as VHL (all exons) and RET (10, 11, 13, 14, 15, 16 exons) genes in all four index cases. A complete clinical, biochemical, and instrumental work-up was performed. Results:Three subjects were found to be affected with a nonsense SDHB germline mutation (Q30X, Y61X, and W201X, respectively). These mutations are predicted to encode for a truncated SDHB protein. The fourth subject presented a S195del frameshift mutation, causing a deletion of the codon AGC, encoding for a serine. Clinical presentation and course of each patient is described. Conclusions: Extra-adrenal paragangliomas, localized in the sympathetic ganglia (in the posterior thorax or in the abdomen), are very often SDHB-inherited form rather than sporadic tumor. Our data confirm the importance of genetic screening in patients affected with paragangliomas and enlarge the list of mutations responsible for the presence of these tumors.
KW - Extra-adrenal paragangliomas
KW - Genetic screening
KW - Germ-line mutations
KW - Succinate dehydrogenase subunit B
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U2 - 10.3389/fendo.2012.00065
DO - 10.3389/fendo.2012.00065
M3 - Article
C2 - 22723792
AN - SCOPUS:84873349175
VL - 3
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
IS - MAY
M1 - Article 65
ER -