d-2-hydroxyglutaric aciduria is a neurometabolic disorder with both a mild and a severe phenotype and with unknown etiology. Recently, a novel enzyme, d-2-hydroxyglutarate dehydrogenase, which converts d-2-hydroxyglutarate into 2-ketoglutarate, and its gene were identified. In the genes of two unrelated patients affected with d-2-hydroxyglutaric aciduria, we identified disease-causing mutations. One patient was homozygous for a missense mutation (c.1331T-->C; p.Val444Ala). The other patient was compound heterozygous for a missense mutation (c.440T-->G; p.Ile147Ser) and a splice-site mutation (IVS1-23A-->G) that resulted in a null allele. Overexpression studies in HEK-293 cells of proteins containing the missense mutations showed a marked reduction of d-2-hydroxyglutarate dehydrogenase activity, proving that mutations in the d-2-hydroxyglutarate dehydrogenase gene cause d-2-hydroxyglutaric aciduria.
Scheda prodotto non validato
Scheda prodotto in fase di analisi da parte dello staff di validazione
|Titolo:||Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria.|
|Rivista:||AMERICAN JOURNAL OF HUMAN GENETICS|
|Citazione:||Struys, E.a., Salomons, G.s., Achouri, Y., Van Schaftingen, E., Grosso, S., Craigen, W.j., et al. (2005). Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. AMERICAN JOURNAL OF HUMAN GENETICS, 76(2), 358-360.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
File in questo prodotto: