IDH2 mutations in patients with D-2-hydroxyglutaric aciduria
(2010) Science — Vol. 330, n° 6002, p. 336 (2010)
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- 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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Kranendijk, M., Struys, E. A., Van Schaftingen, E., Gibson, K. M., Kanhai, W. A., van der Knaap, M. S., Amiel, J., Buist, N. R., Das, A. M., de Klerk, J. B., Feigenbaum, A. S., Grange, D. K., Hofstede, F. C., Holme, E., Kirk, E. P., Korman, S. H., Morava, E., Morris, A., Smeitink, J., et al. (2010). IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. Science, 330(6002), 336. https://doi.org/10.1126/science.1192632 (Original work published 2010)