{"type":"root","children":[{"type":"paragraph","children":[{"type":"text","value":"Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial (SDHB) also known as iron-sulfur subunit of complex II (Ip) is a protein that in humans is encoded by the SDHB gene. The gene that codes for the SDHB protein is nuclear, not mitochondrial DNA. However, the expressed protein is located in the inner membrane of the mitochondria. Four subunits comprise the SDH protein complex: a flavochrome subunit (SDHA), an iron-sulfur protein (SDHB) and two membrane-bound subunits (SDHC and SDHD) anchored to the inner mitochondrial membrane. Mutation in this protein is associated with wide range of diseases such as Renal Cell Carcinoma, Paraganglioma, Gastrointestinal Stromal Tumors (GISTs), Pituitary Adenoma, and many others."}]},{"type":"paragraph","children":[{"type":"text","value":"Mutations in the tumor suppressor genes SDHB, SDHC, and SDHD (or collectively SDHx) cause the inherited paraganglioma syndromes, characterized by pheochromocytomas and paragangliomas. The IHC for SDHB is negative in all SDH mutated paragangliomas regardless of whether the B, C or D subunit is involved. However, other tumors have been associated with SDHx mutations, such as Gastrointestinal Stromal Tumors, specifically in the context of Carney-Stratakis syndrome. It has been shown that SDHB immunohistochemistry is a reliable technique for the identification of pheochromocytomas and paragangliomas caused by SDHx mutations. It’s been shown that Carney-Stratakis syndrome- and Carney-triad-associated GISTs are negative by immunohistochemistry for SDHB in contrast to KIT- or PDGFRA-mutated GISTs and a majority of sporadic GISTs, and it has been suggested that GISTs of epithelioid cell morphology are tested for SDHB immunohistochemically."}]}]}