Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria
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Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. / Nota, Benjamin; Struys, Eduard A; Pop, Ana; Jansen, Erwin E; Fernandez Ojeda, Matilde R; Kanhai, Warsha A; Kranendijk, Martijn; van Dooren, Silvy J M; Bevova, Marianna R; Sistermans, Erik A; Nieuwint, Aggie W M; Barth, Magalie; Ben-Omran, Tawfeg; Hoffmann, Georg F; de Lonlay, Pascale; McDonald, Marie T; Meberg, Alf; Muntau, Ania; Nuoffer, Jean-Marc; Parini, Rossella; Read, Marie-Hélène; Renneberg, Axel; Santer, René; Strahleck, Thomas; van Schaftingen, Emile; van der Knaap, Marjo S; Jakobs, Cornelis; Salomons, Gajja S.
in: AM J HUM GENET, Jahrgang 92, Nr. 4, 04.04.2013, S. 627-31.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria
AU - Nota, Benjamin
AU - Struys, Eduard A
AU - Pop, Ana
AU - Jansen, Erwin E
AU - Fernandez Ojeda, Matilde R
AU - Kanhai, Warsha A
AU - Kranendijk, Martijn
AU - van Dooren, Silvy J M
AU - Bevova, Marianna R
AU - Sistermans, Erik A
AU - Nieuwint, Aggie W M
AU - Barth, Magalie
AU - Ben-Omran, Tawfeg
AU - Hoffmann, Georg F
AU - de Lonlay, Pascale
AU - McDonald, Marie T
AU - Meberg, Alf
AU - Muntau, Ania
AU - Nuoffer, Jean-Marc
AU - Parini, Rossella
AU - Read, Marie-Hélène
AU - Renneberg, Axel
AU - Santer, René
AU - Strahleck, Thomas
AU - van Schaftingen, Emile
AU - van der Knaap, Marjo S
AU - Jakobs, Cornelis
AU - Salomons, Gajja S
N1 - Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
PY - 2013/4/4
Y1 - 2013/4/4
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Anion Transport Proteins
KW - Biological Markers
KW - Brain Diseases, Metabolic, Inborn
KW - Case-Control Studies
KW - Cells, Cultured
KW - Chromatography, Liquid
KW - Citric Acid
KW - Exome
KW - Female
KW - Fibroblasts
KW - Genes, Recessive
KW - Glutarates
KW - Humans
KW - Male
KW - Mitochondria
KW - Mitochondrial Proteins
KW - Molecular Sequence Data
KW - Mutation
KW - Phenotype
KW - Protein Structure, Tertiary
KW - Retrospective Studies
KW - Sequence Homology, Amino Acid
KW - Stereoisomerism
KW - Tandem Mass Spectrometry
U2 - 10.1016/j.ajhg.2013.03.009
DO - 10.1016/j.ajhg.2013.03.009
M3 - SCORING: Journal article
C2 - 23561848
VL - 92
SP - 627
EP - 631
JO - AM J HUM GENET
JF - AM J HUM GENET
SN - 0002-9297
IS - 4
ER -