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Mutations associated with succinate dehydrogenase d ‐related malignant paragangliomas
Author(s) -
Timmers Henri J. L. M.,
Pacak Karel,
Bertherat Jérôme,
Lenders Jacques W. M.,
Duet Michèle,
Eisenhofer Graeme,
Stratakis Constantine A.,
NiccoliSire Patricia,
Huy Patrice Tran Ba,
Burnichon Nelly,
GimenezRoqueplo AnnePaule
Publication year - 2008
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2007.03086.x
Subject(s) - sdhd , sdhb , paraganglioma , germline mutation , mutation , pheochromocytoma , medicine , succinate dehydrogenase , germline , endocrinology , genetics , biology , cancer research , sdha , gene , mitochondrion , pathology
Summary Objective  Hereditary paraganglioma (PGL) syndromes result from germline mutations in genes encoding subunits B, C and D of the mitochondrial enzyme succinate dehydrogenase (SDHB, SDHC and SDHD). SDHB‐ related PGLs are known in particular for their high malignant potential. Recently, however, malignant PGLs were also reported among a small minority of Dutch carriers of the SDHD founder mutation D92Y. The aim of the study was to investigate which SDHD mutations are associated with malignant PGL. Design  Case histories; collaborative study between referral centres in France, the USA, and the Netherlands. Patients  Six unrelated patients with metastatic PGLs of either sympathetic or parasympathetic origin. Measurements  Assessment of SDHD mutations underlying malignant PGL. Results  Germline S DHD mutations underlying metastatic PGL were G148D, Y114X, L85X, W43X, D92Y, and IVS2+5G→A. Conclusion  Our findings indicate that malignant SDHD‐ related PGL is associated with several mutations besides D92Y.

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