Mutations associated with succinate dehydrogenase D-related malignant paragangliomas

Abstract

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.