Mutations of the SDHB and SDHD genes.
The succinate dehydrogenase (SDH) is a mitochondrial enzyme complex with an important role in oxydative phosphorylation and intracellular oxygene sensing and signaling. Mutations in the SDHB (1p35-36) and SDHD subunits (11q23) give rise to the paraganglioma syndromes (PGL), namely PGL 4 and PGL 1, and generate paraganglioma and pheochromocytoma. For both genes mutations have been described that result in a loss of function of the gene products. SDHBmutations were found in five of eight exons and in two introns, SDHD mutations in all four exons and one intron. Phenotypes and rate of malignancy of SDHB and SDHD seem to be different, with a higher frequency of head-and-neck tumors in SDHD and indications of a higher risk of malignancy in SDHB mutations. As routine diagnostic procedure all SDH mutation carriers should have urine catecholamine analysis as well as pelvic, abdominal, thoracic and skull/neck MRI.
Pawlu
Christian
C
Department of Nephrology and Hypertension, Albert-Ludwigs-Universität, Freiburg, Germany.
Bausch
Birke
B
Neumann
Hartmut P H
HP
D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010235:Paraganglioma / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D010641:Phenotype; D010673:Pheochromocytoma / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics*; D012307:Risk Factors; D013385:Succinate Dehydrogenase / Q000235:genetics*
D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; C491545:SDHD protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase