IDH2 mutations in patients with D-2-hydroxyglutaric aciduria

Martijn Kranendijk, Eduard A. Struys, Emile Van Schaftingen, K. Michael Gibson, Warsha A. Kanhai, Marjo S. Van Der Knaap, Jeanne Amiel, Neil R. Buist, Anibh M. Das, Johannis B. De Klerk, Annette S. Feigenbaum, Dorothy K. Grange, Floris C. Hofstede, Elisabeth Holme, Edwin P. Kirk, Stanley H. Korman, Eva Morava, Andrew Morris, Jan Smeitink, Rám N. SukhaiHilary Vallance, Cornelis Jakobs, Gajja S. Salomons

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
JournalScience
Volume330
Issue number6002
DOIs
Publication statusPublished - 15 Oct 2010

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