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dc.contributor.authorPop, Ana
dc.contributor.authorWilliams, Monique
dc.contributor.authorStruys, Eduard A
dc.contributor.authorMonne, Magnus
dc.contributor.authorJansen, Erwin EW
dc.contributor.authorDe Grassi, Anna
dc.contributor.authorKanhai, Warsha A
dc.contributor.authorScarcia, Pasquale
dc.contributor.authorOjed, Matilde R Fernandez
dc.contributor.authorPorcelli, Vito
dc.contributor.authorvan Dooren, Silvy JM
dc.contributor.authorLennertz, Pascal
dc.contributor.authorNota, Benjamin
dc.contributor.authorAbdenur, Jose E
dc.contributor.authorComan, David
dc.contributor.authorDas, Anibh Martin
dc.contributor.authorEl-Gharbawy, Areeg
dc.contributor.authorNuoffer, Jean-Marc
dc.contributor.authorPolic, Branka
dc.contributor.authorSanter, Rene
dc.contributor.authorWeinhold, Natalie
dc.contributor.authorZuccarelli, Britton
dc.contributor.authorPalmieri, Ferdinando
dc.contributor.authorPalmieri, Luigi
dc.contributor.authorSalomons, Gajja S
dc.date.accessioned2019-07-05T12:32:42Z
dc.date.available2019-07-05T12:32:42Z
dc.date.issued2018
dc.identifier.issn0141-8955
dc.identifier.doi10.1007/s10545-017-0106-7
dc.identifier.urihttp://hdl.handle.net/10072/371537
dc.description.abstractCombined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA) is a devastating neurometabolic disorder, usually lethal in the first years of life. Autosomal recessive mutations in the SLC25A1 gene, which encodes the mitochondrial citrate carrier (CIC), were previously detected in patients affected with combined D/L-2-HGA. We showed that transfection of deficient fibroblasts with wild-type SLC25A1 restored citrate efflux and decreased intracellular 2-hydroxyglutarate levels, confirming that deficient CIC is the cause of D/L-2-HGA. We developed and implemented a functional assay and applied it to all 17 missense variants detected in a total of 26 CIC-deficient patients, including eight novel cases, showing reduced activities of varying degrees. In addition, we analyzed the importance of residues affected by these missense variants using our existing scoring system. This allowed not only a clinical and biochemical overview of the D/L-2-HGA patients but also phenotype–genotype correlation studies.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherSpringer Netherlands
dc.publisher.placeNetherlands
dc.relation.ispartofpagefrom169
dc.relation.ispartofpageto180
dc.relation.ispartofissue2
dc.relation.ispartofjournalJournal of Inherited Metabolic Disease
dc.relation.ispartofvolume41
dc.subject.fieldofresearchClinical Sciences not elsewhere classified
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchcode110399
dc.subject.fieldofresearchcode1103
dc.titleAn overview of combined D-2- and L-2-hydroxyglutaric aciduria: functional analysis of CIC variants
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionPublished
gro.rights.copyright© The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
gro.hasfulltextFull Text
gro.griffith.authorComan, Dave J.


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