dc.contributor.author | Pop, Ana | |
dc.contributor.author | Williams, Monique | |
dc.contributor.author | Struys, Eduard A | |
dc.contributor.author | Monne, Magnus | |
dc.contributor.author | Jansen, Erwin EW | |
dc.contributor.author | De Grassi, Anna | |
dc.contributor.author | Kanhai, Warsha A | |
dc.contributor.author | Scarcia, Pasquale | |
dc.contributor.author | Ojed, Matilde R Fernandez | |
dc.contributor.author | Porcelli, Vito | |
dc.contributor.author | van Dooren, Silvy JM | |
dc.contributor.author | Lennertz, Pascal | |
dc.contributor.author | Nota, Benjamin | |
dc.contributor.author | Abdenur, Jose E | |
dc.contributor.author | Coman, David | |
dc.contributor.author | Das, Anibh Martin | |
dc.contributor.author | El-Gharbawy, Areeg | |
dc.contributor.author | Nuoffer, Jean-Marc | |
dc.contributor.author | Polic, Branka | |
dc.contributor.author | Santer, Rene | |
dc.contributor.author | Weinhold, Natalie | |
dc.contributor.author | Zuccarelli, Britton | |
dc.contributor.author | Palmieri, Ferdinando | |
dc.contributor.author | Palmieri, Luigi | |
dc.contributor.author | Salomons, Gajja S | |
dc.date.accessioned | 2019-07-05T12:32:42Z | |
dc.date.available | 2019-07-05T12:32:42Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 0141-8955 | |
dc.identifier.doi | 10.1007/s10545-017-0106-7 | |
dc.identifier.uri | http://hdl.handle.net/10072/371537 | |
dc.description.abstract | Combined 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Springer Netherlands | |
dc.publisher.place | Netherlands | |
dc.relation.ispartofpagefrom | 169 | |
dc.relation.ispartofpageto | 180 | |
dc.relation.ispartofissue | 2 | |
dc.relation.ispartofjournal | Journal of Inherited Metabolic Disease | |
dc.relation.ispartofvolume | 41 | |
dc.subject.fieldofresearch | Clinical Sciences not elsewhere classified | |
dc.subject.fieldofresearch | Clinical Sciences | |
dc.subject.fieldofresearchcode | 110399 | |
dc.subject.fieldofresearchcode | 1103 | |
dc.title | An overview of combined D-2- and L-2-hydroxyglutaric aciduria: functional analysis of CIC variants | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
dcterms.license | http://creativecommons.org/licenses/by/4.0/ | |
dc.description.version | Published | |
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.hasfulltext | Full Text | |
gro.griffith.author | Coman, Dave J. | |