IDH2 Mutations in Patients with d -2-Hydroxyglutaric Aciduria

• DOI: 10.1126/science.1192632
• Publication Date: 2010-09-17T04:16:06Z
• Authors: Martijn Kranendijk; Eduard A. Struys; Emile van Schafti...; K. Michael Gibson; Warsha A. Kanhai; Marjo S. van der ...; Jeanne Amiel; Neil R. Buist; Anibh M. Das; Johannis B. de Klerk; Annette S. Feigen...; Dorothy K. Grange; Floris C. Hofstede; Elisabeth Holme; Edwin P. Kirk; Stanley H. Korman; Eva Morava; Andrew Morris; Jan Smeitink; Rám N. Sukhai; Hilary Vallance; Cornelis Jakobs; Gajja S. Salomons
• Keywords: Isocitrate dehydrogenase; IDH2

Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase-1 and -2 (IDH1 IDH2) were recently discovered human neoplastic disorders. These disable enzymes' normal ability to convert 2-ketoglutarate (2-KG) confer on enzymes a new function: 2-KG d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline IDH2 that alter enzyme residue Arg(140) 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. findings provide additional impetus for investigating role D-2-HG pathophysiology metabolic disease cancer.