D-2-hydroxyglutaric aciduria Type I: Functional analysis of D2HGDH missense variants.

ABSTRACT: D-2-hydroxyglutaric aciduria Type I (D-2-HGA Type I), a neurometabolic disorder with a broad clinical spectrum, is caused by recessive variants in the D2HGDH gene encoding D-2-hydroxyglutarate dehydrogenase (D-2-HGDH). We and others detected 42 potentially pathogenic variants in D2HGDH of which 31 were missense. We developed functional studies to investigate the effect of missense variants on D-2-HGDH catalytic activity. Site-directed mutagenesis was used to introduce 31 missense variants in the pCMV5-D2HGDH expression vector. The wild type and missense variants were overexpressed in HEK293 cells. D-2-HGDH enzyme activity was evaluated based on the conversion of [² H₄ ]D-2-HG to [² H₄ ]2-ketoglutarate, which was subsequently converted into [

SUBMITTER: Pop A 

PROVIDER: S-EPMC6619364 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature