IDH2 Mutations in Patients with d-2-Hydroxyglutaric Aciduria
Abstract
Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase-1 and -2 (IDH1 and IDH2) were recently discovered in human neoplastic disorders. These mutations disable the enzymes’ normal ability to convert isocitrate to 2-ketoglutarate (2-KG) and confer on the enzymes a new function: the ability to convert 2-KG to d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline mutations in IDH2 that alter enzyme residue Arg140 in 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. These findings provide additional impetus for investigating the role of D-2-HG in the pathophysiology of metabolic disease and cancer.
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Science
Volume 330 | Issue 6002
15 October 2010
15 October 2010
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Copyright © 2010, American Association for the Advancement of Science.
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Received: 21 May 2010
Accepted: 11 August 2010
Published in print: 15 October 2010
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- Martijn Kranendijk et al.
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