Mutations in phenotypically mild D-2-hydroxyglutaric aciduria.
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.
Struys
Eduard A
EA
Metabolic Unit, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
Korman
Stanley H
SH
Salomons
Gajja S
GS
Darmin
Patricia S
PS
Achouri
Younes
Y
van Schaftingen
Emile
E
Verhoeven
Nanda M
NM
Jakobs
Cornelis
C
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
D004274:DNA, Recombinant; D000429:Alcohol Oxidoreductases; C023858:2-hydroxyglutarate dehydrogenase