SdhB

SDHB, or succinate dehydrogenase complex iron-sulfur subunit B, is a protein encoded by the SDHB gene in humans. It is one of the four nuclear-encoded subunits of mitochondrial complex II (succinate dehydrogenase) that participates in both the Krebs cycle and the mitochondrial electron transport chain.

SDHB contains iron-sulfur clusters essential for electron transfer from succinate to ubiquinone. As part of complex II, it helps catalyze the oxidation of succinate to fumarate and links the Krebs cycle to the respiratory chain. The protein’s proper function is required for efficient energy production in mitochondria.

SDHB is located on chromosome 1p36.13. Pathogenic variants in SDHB are associated with hereditary paraganglioma-pheochromocytoma syndromes (PGL/PCC). Inheritance is autosomal dominant with variable penetrance; tumors can arise in the head and neck, thorax, abdomen, or pelvis. SDHB mutations are particularly linked to extra-adrenal paragangliomas and a higher risk of malignancy compared with other SDHx genes.

In tumor diagnostics, loss of SDHB immunohistochemical staining is a surrogate marker for SDHx-deficient tumors, guiding genetic testing and management. Biochemical testing for catecholamine excess and targeted imaging are used to locate and characterize tumors.

Management includes genetic counseling and testing for affected individuals and at-risk relatives, regular surveillance with imaging and biochemical monitoring, and treatment through surgical resection when feasible. Long-term follow-up is recommended due to the potential for multifocal disease and late recurrences.