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- Title
SDH Mutations in Patients Affected by Paraganglioma Syndromes.
- Authors
MANNELLI, M.; SIMI, L.; ERCOLINO, T.; GAGLIANÒ, M.S.; BECHERINI, L.; VINCI, S.; SESTINI, R.; GENSINI, F.; PINZANI, P.; MASCALCHI, M.; GUERRINI, L.; PRATESI, C.; NESI, G.; TORTI, F.; CIPOLLINI, F.; BERNINI, G.P.; GENUARDI, M.
- Abstract
Mutations in genes encoding mitochondrial succinate dehydrogenase (SDH) are frequently involved in the development of neural crest-derived (NCD) tumors, such as pheochromocytomas (PHEOs) or paragangliomas (PGLs). In this study we report the results of sequencing analysis in leukocyte DNA of patients affected by PHEO/PGL who turned out to be SDH mutation carriers. A nonsense germline heterozygous mutation (Q109X) was found in the exon 4 of the SDHD gene in the index cases of six unrelated families affected by PHEO/PGL. Haplotype analysis showed the presence of a founder effect. Affected patients showed high clinical variability, ranging from monolateral to bilateral glomus tumors, variably associated or not with PGLs or PHEOs. A novel missense SDHD variant, T112I, was also found in one of our families. A new missense G106D mutation, involving a highly conserved amino acid, was found in two sisters affected by bilateral glomus tumors. A P81L mutation associated with abdominal and head and neck PGL was detected in three families. A G12S variant of the SDHD gene was found in one patient affected by a PHEO. The finding of this variant in 3 of 100 control subjects suggests that it is a polymorphism and not a mutation. A novel IVS2-1G>T variant was found at intron 2 of SDHD gene in one patient affected by a glomus tumor. All the tumors associated with SDHD mutations were benign. Conversely, the only mutation we found in SDHB gene (IVS3 + 1G>A) was associated with a malignant PHEO.
- Subjects
NONCHROMAFFIN paraganglioma; GENES; SUCCINATE dehydrogenase; PHEOCHROMOCYTOMA; TUMORS
- Publication
Annals of the New York Academy of Sciences, 2006, Vol 1073, Issue 1, p183
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1196/annals.1353.019