Mutations in <i>SDHD</i> , a Mitochondrial Complex II Gene, in Hereditary Paraganglioma

TLDR

Hereditary paraganglioma is a benign, vascularized tumor of the head and neck, most commonly arising in the carotid body, and involves the SDHD gene encoding a mitochondrial respiratory chain protein. The study identified germ‑line SDHD mutations in families with PGL1 by analyzing affected pedigrees. The SDHD mutations were not imprinted, underscoring a mitochondrial contribution to tumorigenesis and suggesting a role for cybS in normal carotid body function.

Abstract

Hereditary paraganglioma (PGL) is characterized by the development of benign, 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, revealed germ line mutations in the SDHD gene on chromosome 11q23. SDHD encodes a mitochondrial respiratory chain protein—the small subunit of cytochrome b in succinate-ubiquinone oxidoreductase (cybS). In contrast to expectations based on the inheritance pattern of PGL, the SDHD gene showed no evidence of imprinting. These findings indicate that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology.