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Published on: May 17, 2024
Mutations associated with succinate dehydrogenase D-related malignant paragangliomas
Henri J L M Timmers1, Karel Pacak, Jérôme Bertherat
1Reproductive 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
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 SDHD 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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