title: Mutations in phenotypically mild D-2-hydroxyglutaric aciduria.
abstract: D-2-hydroxyglutaric aciduria is a neurometabolic disorder with mild and severe phenotypes. Recently, we reported pathogenic mutations in the D-2-hydroxyglutarate dehydrogenase gene as the cause of the severe phenotype of D-2-hydroxyglutaric aciduria in two patients. Here, we report two novel pathogenic mutations in this gene in one patient with a mild presentation and two asymptomatic siblings with D-2-hydroxyglutaric aciduria from two unrelated consanguineous Palestinian families: a splice error (IVS4-2A-->G) and a missense mutation (c.1315A-->G;p.Asn439Asp). Overexpression of this mutant protein showed marked reduction of the enzyme activity.
authors.affiliation: Metabolic Unit, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Eduard A
authors.initials: EA
authors.lastname: Struys
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Korman
authors.forename: Gajja S
authors.initials: GS
authors.lastname: Salomons
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Darmin
authors.forename: Younes
authors.initials: Y
authors.lastname: Achouri
authors.forename: Emile
authors.initials: E
authors.lastname: van Schaftingen
authors.forename: Nanda M
authors.initials: NM
authors.lastname: Verhoeven
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000652:urine*; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D004274:DNA, Recombinant; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D004274:DNA, Recombinant; D000429:Alcohol Oxidoreductases; C023858:2-hydroxyglutarate dehydrogenase