Mutations associated with succinate dehydrogenase d‐related malignant paragangliomas

Abstract

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. Case histories; collaborative study between referral centres in France, the USA, and the Netherlands. Six unrelated patients with metastatic PGLs of either sympathetic or parasympathetic origin. Assessment of SDHD mutations underlying malignant PGL. Germline SDHD mutations underlying metastatic PGL were G148D, Y114X, L85X, W43X, D92Y, and IVS2+5G-->A. Our findings indicate that malignant SDHD-related PGL is associated with several mutations besides D92Y.