IDH2 mutations in patients with D-2-hydroxyglutaric aciduria
- Kranendijk, Martijn
- Struys, Eduard A
- Van Schaftingen, Emile
- Gibson, K Michael
- Kanhai, Warsha A
- van der Knaap, Marjo S
- Amiel, Jeanne
- Buist, Neil R
- Das, Anibh M
- de Klerk, Johannis B
- Feigenbaum, Annette S
- Grange, Dorothy K
- Hofstede, Floris C
- Holme, Elisabeth
- Kirk, Edwin P
- Korman, Stanley H
- Morava, Eva
- Morris, Andrew
- Smeitink, Jan
- Sukhai, Rám N
- Vallance, Hilary
- Jakobs, Cornelis
- Salomons, Gajja S
Publication date
January 2010
DOI Publisher
American Association for the Advancement of Science (AAAS)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 Arg(140) 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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