title: Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.
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.
authors.affiliation: Department of Psychiatry, The University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2593, USA. baysalbe@msx.upmc.edu
authors.forename: B E
authors.initials: BE
authors.lastname: Baysal
authors.forename: R E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: J E
authors.initials: JE
authors.lastname: Willett-Brozick
authors.forename: E C
authors.initials: EC
authors.lastname: Lawrence
authors.forename: D
authors.initials: D
authors.lastname: Myssiorek
authors.forename: A
authors.initials: A
authors.lastname: Bosch
authors.forename: A
authors.initials: A
authors.lastname: van der Mey
authors.forename: P E
authors.initials: PE
authors.lastname: Taschner
authors.forename: W S
authors.initials: WS
authors.lastname: Rubinstein
authors.forename: E N
authors.initials: EN
authors.lastname: Myers
authors.forename: C W
authors.initials: CW
authors.lastname: Richard
authors.forename: C J
authors.initials: CJ
authors.lastname: Cornelisse
authors.forename: P
authors.initials: P
authors.lastname: Devilee
authors.forename: B
authors.initials: B
authors.lastname: Devlin
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D002344:Carotid Body / Q000378:metabolism; D002345:Carotid Body Tumor / Q000235:genetics* / Q000378:metabolism; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003573:Cytochrome b Group / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D042963:Electron Transport Complex II; D008040:Genetic Linkage; D018392:Genomic Imprinting; D018095:Germ-Line Mutation; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010235:Paraganglioma / Q000235:genetics* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D013385:Succinate Dehydrogenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D003573:Cytochrome b Group; D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase