Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma

Hereditary paraganglioma (PGL) is characterized by the development of benig n, vascularized tumors in the head and neck. The most common tumor site is the carotid body (CB), a chemoreceptive organ that senses oxygen Levels in the blood. Analysis of families carrying the PGL1 gene, described here, rev ealed germ line mutations in the SDHD gene on chromosome 11q23. SDHD encode s a mitochondrial respiratory chain protein-the small subunit of cytochrome b in succinate-ubiquinone oxidoreductase (cybS). In contrast to expectatio ns based on the inheritance pattern of PGL, the SDHD gene showed no evidenc e of imprinting. These findings indicate that mitochondria play an importan t role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology.