Gene SDHD
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Also known as
Succinate Dehydrogenase Complex Subunit D, CBT1, PGL, PGL1, SDH4Overview
SDHD (Succinate Dehydrogenase Complex Subunit D) encodes one of two integral membrane anchor subunits of the succinate dehydrogenase (SDH) complex in mitochondria. Together with SDHC, the SDHD protein anchors the catalytic core of the complex to the inner mitochondrial membrane, where it functions as both a key enzyme in the citric acid cycle and as complex II of the electron transport chain. SDHD plays an essential role in transferring electrons from the oxidation of succinate to ubiquinone in the respiratory chain, thereby participating in cellular energy production.Mutations in SDHD are the most common cause of hereditary head and neck paragangliomas (HNPGLs), benign tumors arising from parasympathetic ganglia, particularly carotid body tumors. SDHD-related paraganglioma syndrome (PGL1) exhibits a unique parent-of-origin effect: tumors typically develop only when the mutation is inherited from the father (paternal transmission), due to maternal imprinting of the gene. Affected individuals often develop multiple paragangliomas at young ages and may also develop pheochromocytomas and, less commonly, renal cell carcinoma. While these tumors are usually benign, they can cause significant morbidity through mass effects and catecholamine excess. Genetic testing for SDHD mutations is crucial for surveillance planning, surgical management, and understanding familial inheritance patterns in affected families.