Mutations in phenotypically mild-D-2-hydroxyglutaric aciduria

VU University Amsterdam, Amsterdamo, North Holland, Netherlands
Annals of Neurology (Impact Factor: 11.91). 10/2005; 58(4):626-30. DOI: 10.1002/ana.20559
Source: PubMed

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.

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    06/2010, Degree: Dr. rer. nat. (PhD), Supervisor: Ulf-Ingo Fluegge and Veronica G. Maurino