Mutations in SDHD, A Mitochondrial Complex II Gene, in Hereditary Paraganglioma

• Published in: Science (American Association for the Advancement of Science) 2000-02, Vol.287 (5454), p.848-851
• Main Authors: Baysal, Bora E., Ferrell, Robert E., Willett-Brozick, Joan E., Lawrence, Elizabeth C., Myssiorek, David, Bosch, Anne, van der Mey, Andel, Peter E. M. Taschner, Rubinstein, Wendy S., Myers, Eugene N., Richard, Charles W., Cornelisse, Cees J., Devilee, Peter, Devlin, B.
• Format: Article
• Language: English
• Subjects: Alleles; Amino Acid Sequence; Anoxia; Bee dances; Biological and medical sciences; carotid body; Carotid Body - metabolism; Carotid Body Tumor - genetics; Carotid Body Tumor - metabolism; Chromosomes; Chromosomes, Human, Pair 11 - genetics; cybS protein; cytochrome b; Cytochrome b Group - chemistry; Cytochrome b Group - genetics; Cytochrome b Group - metabolism; Electron Transport Complex II; Exons; Family (Sociological Unit); Genes; Genetic Disorders; Genetic Linkage; Genetic mutation; Genomic Imprinting; Genomics; Germ-Line Mutation; Haplotypes; Heterozygote; Honey bees; Humans; Hypoxia; Loss of Heterozygosity; Medical sciences; Mitochondria - metabolism; Molecular Sequence Data; Multienzyme Complexes - chemistry; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; Mutation; Mutation (Biology); Mutation, Missense; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Oxidoreductases - chemistry; Oxidoreductases - genetics; Oxidoreductases - metabolism; Oxygen; paraganglioma; Paraganglioma - genetics; Paraganglioma - metabolism; Polymorphism, Single-Stranded Conformational; Proteins; SBHD gene; Scientific Concepts; Succinate Dehydrogenase - chemistry; Succinate Dehydrogenase - genetics; Succinate Dehydrogenase - metabolism; Transcripts (Written Records); Tumors
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.287.5454.848

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.