What question did this study set out to answer?

To identify the underlying biochemical mechanism and genetic defect responsible for L-2-hydroxyglutaric aciduria.

November 17, 2004Proceedings of the National Academy of SciencesOpen Access

A gene encoding a putative FAD-dependent l -2-hydroxyglutarate dehydrogenase is mutated in l -2-hydroxyglutaric aciduria

View Full Paper

Ask AI

Bookmark

Authors

RRRzem Rimde Duve Institute MVMaria Veiga‐da‐Cunhade Duve Institute GNG. NoëlLevi Strauss (United States)

Discussion

Member takes

Implication

Genetic and biochemical analysis reveals mutations in a mitochondrial dehydrogenase gene in patients with L-2-hydroxyglutaric aciduria, indicating metabolic toxicity drives neurological damage.

Key Points

To identify the underlying biochemical mechanism and genetic defect responsible for L-2-hydroxyglutaric aciduria.
Assayed rat tissues and subcellular fractions to identify and localize enzymatic oxidation of L-2-hydroxyglutarate to alpha-ketoglutarate.
Identified candidate human genes on chromosome 14q22.1 using database homology searches for mitochondrial FAD-dependent dehydrogenases.
Performed sequence analysis of the candidate gene in affected individuals from consanguineous families with L-2-hydroxyglutaric aciduria.
Identified a membrane-bound mitochondrial enzyme in rat liver and kidney that specifically catalyzes FAD-dependent oxidation of L-2-hydroxyglutarate to alpha-ketoglutarate.
Mapped a homologous human mitochondrial protein gene to a homozygous disease region on chromosome 14q22.1.
Detected three homozygous mutations (Lys-71-Glu, Glu-176-Asp, and an exon 9 deletion) that cosegregated with L-2-hydroxyglutaric aciduria across three distinct families.

Cite This Study

Rim et al. (2004) studied this question.

synapsesocial.com/papers/69d8fe2398a648f070ae2b08 https://doi.org/10.1073/pnas.0404840101

View Full Paper

Ask AI

Bookmark

Implication

Genetic and biochemical analysis reveals mutations in a mitochondrial dehydrogenase gene in patients with L-2-hydroxyglutaric aciduria, indicating metabolic toxicity drives neurological damage.

A gene encoding a putative FAD-dependent l -2-hydroxyglutarate dehydrogenase is mutated in l -2-hydroxyglutaric aciduria

Discussion

Member takes

Implication

Key Points

Cite This Study

A gene encoding a putative FAD-dependent l -2-hydroxyglutarate dehydrogenase is mutated in l -2-hydroxyglutaric aciduria

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider