Mutations associated with succinate dehydrogenase D-related malignant paragangliomas.
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.


METHODS
Case histories; collaborative study between referral centres in France, the USA, and the Netherlands.


METHODS
Six unrelated patients with metastatic PGLs of either sympathetic or parasympathetic origin.


METHODS
Assessment of SDHD mutations underlying malignant PGL.


RESULTS
Germline SDHD mutations underlying metastatic PGL were G148D, Y114X, L85X, W43X, D92Y, and IVS2+5G-->A.


CONCLUSIONS
Our findings indicate that malignant SDHD-related PGL is associated with several mutations besides D92Y.
Timmers
Henri J L M
HJ
Reproductive Biology and Adult Endocrinology Program, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1109, USA. h.timmers@endo.umcn.nl
Pacak
Karel
K
Bertherat
Jérôme
J
Lenders
Jacques W M
JW
Duet
Michèle
M
Eisenhofer
Graeme
G
Stratakis
Constantine A
CA
Niccoli-Sire
Patricia
P
Tran
Ba Huy Patrice
BH
Burnichon
Nelly
N
Gimenez-Roqueplo
Anne-Paule
AP
D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009423:Nervous System Neoplasms / Q000201:enzymology / Q000235:genetics*; D010235:Paraganglioma / Q000201:enzymology / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
C491545:SDHD protein, human; D013385:Succinate Dehydrogenase