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Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.

Publication ,  Journal Article
Nota, B; Struys, EA; Pop, A; Jansen, EE; Fernandez Ojeda, MR; Kanhai, WA; Kranendijk, M; van Dooren, SJM; Bevova, MR; Sistermans, EA; Barth, M ...
Published in: Am J Hum Genet
April 4, 2013

The Krebs cycle is of fundamental importance for the generation of the energetic and molecular needs of both prokaryotic and eukaryotic cells. Both enantiomers of metabolite 2-hydroxyglutarate are directly linked to this pivotal biochemical pathway and are found elevated not only in several cancers, but also in different variants of the neurometabolic disease 2-hydroxyglutaric aciduria. Recently we showed that cancer-associated IDH2 germline mutations cause one variant of 2-hydroxyglutaric aciduria. Complementary to these findings, we now report recessive mutations in SLC25A1, the mitochondrial citrate carrier, in 12 out of 12 individuals with combined D-2- and L-2-hydroxyglutaric aciduria. Impaired mitochondrial citrate efflux, demonstrated by stable isotope labeling experiments and the absence of SLC25A1 in fibroblasts harboring certain mutations, suggest that SLC25A1 deficiency is pathogenic. Our results identify defects in SLC25A1 as a cause of combined D-2- and L-2-hydroxyglutaric aciduria.

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Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

April 4, 2013

Volume

92

Issue

4

Start / End Page

627 / 631

Location

United States

Related Subject Headings

  • Tandem Mass Spectrometry
  • Stereoisomerism
  • Sequence Homology, Amino Acid
  • Retrospective Studies
  • Protein Structure, Tertiary
  • Phenotype
  • Organic Anion Transporters
  • Mutation
  • Molecular Sequence Data
  • Mitochondrial Proteins
 

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Nota, B., Struys, E. A., Pop, A., Jansen, E. E., Fernandez Ojeda, M. R., Kanhai, W. A., … Salomons, G. S. (2013). Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. Am J Hum Genet, 92(4), 627–631. https://doi.org/10.1016/j.ajhg.2013.03.009
Nota, Benjamin, Eduard A. Struys, Ana Pop, Erwin E. Jansen, Matilde R. Fernandez Ojeda, Warsha A. Kanhai, Martijn Kranendijk, et al. “Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.Am J Hum Genet 92, no. 4 (April 4, 2013): 627–31. https://doi.org/10.1016/j.ajhg.2013.03.009.
Nota B, Struys EA, Pop A, Jansen EE, Fernandez Ojeda MR, Kanhai WA, et al. Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. Am J Hum Genet. 2013 Apr 4;92(4):627–31.
Nota, Benjamin, et al. “Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.Am J Hum Genet, vol. 92, no. 4, Apr. 2013, pp. 627–31. Pubmed, doi:10.1016/j.ajhg.2013.03.009.
Nota B, Struys EA, Pop A, Jansen EE, Fernandez Ojeda MR, Kanhai WA, Kranendijk M, van Dooren SJM, Bevova MR, Sistermans EA, Nieuwint AWM, Barth M, Ben-Omran T, Hoffmann GF, de Lonlay P, McDonald MT, Meberg A, Muntau AC, Nuoffer J-M, Parini R, Read M-H, Renneberg A, Santer R, Strahleck T, van Schaftingen E, van der Knaap MS, Jakobs C, Salomons GS. Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. Am J Hum Genet. 2013 Apr 4;92(4):627–631.
Journal cover image

Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

April 4, 2013

Volume

92

Issue

4

Start / End Page

627 / 631

Location

United States

Related Subject Headings

  • Tandem Mass Spectrometry
  • Stereoisomerism
  • Sequence Homology, Amino Acid
  • Retrospective Studies
  • Protein Structure, Tertiary
  • Phenotype
  • Organic Anion Transporters
  • Mutation
  • Molecular Sequence Data
  • Mitochondrial Proteins