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 cance
Add to ORKG