Krause, Cindy

[["dc.bibliographiccitation.firstpage","869"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Inherited Metabolic Disease"],["dc.bibliographiccitation.lastpage","876"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Dechent, Peter"],["dc.contributor.author","Krause, Cindy"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:44:32Z"],["dc.date.available","2017-09-07T11:44:32Z"],["dc.date.issued","2016"],["dc.description.abstract","Defects in the biogenesis of peroxisomes cause a clinically and genetically heterogeneous group of neurometabolic disorders, the Zellweger syndrome spectrum (ZSS). Diagnosis predominantly is based on characteristic clinical symptoms, a typical biochemical profile, as well as on identification of the molecular defect in any of the 12 known human PEX genes. The diagnostic workup can be hindered if the typical clinical symptoms are missing and predicting the clinical course of a given patient is almost unfeasible. As a safe and noninvasive method to analyze specific chemical compounds in localized brain regions, in vivo proton magnetic resonance spectroscopy (MRS) can provide an indication in this diagnostic process and may help predict the clinical course. However, to date, there are very few reports on this topic. In this study, we performed localized in vivo proton MRS without confounding contributions from T1- and T2-relaxation effects at 2 Tesla in a comparably large group of seven ZSS patients. Patients' absolute metabolite concentrations in cortical gray matter, white matter, and basal ganglia were assessed and compared with age-matched control values. Our results confirm and extend knowledge about in vivo MRS findings in ZSS patients. Besides affirmation of nonspecific reduction of N-acetylaspartate + N-acetylaspartylglutamate (tNAA) in combination with lipid accumulation as a diagnostic hint for this disease group, the amount of tNAA loss seems to reflect disease burden and may prove to be of prognostic value regarding the clinical course of an already diagnosed patient."],["dc.identifier.doi","10.1007/s10545-016-9965-6"],["dc.identifier.gro","3141599"],["dc.identifier.isi","000386383500011"],["dc.identifier.pmid","27488561"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/10"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.relation.eissn","1573-2665"],["dc.relation.issn","0141-8955"],["dc.title","Diagnostic and prognostic value of in vivo proton MR spectroscopy for Zellweger syndrome spectrum patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3844"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","3857"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Krause, Cindy"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Woehler, Andrew"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:47:08Z"],["dc.date.available","2017-09-07T11:47:08Z"],["dc.date.issued","2013"],["dc.description.abstract","In humans, the concerted action of at least 13 different peroxisomal PEX proteins is needed for proper peroxisome biogenesis. Mutations in any of these PEX genes can lead to lethal neurometabolic disorders of the Zellweger syndrome spectrum (ZSS). Previously, we identified the W313G mutation located within the SH3 domain of the peroxisomal protein, PEX13. As this tryptophan residue is highly conserved in almost all known SH3 proteins, we investigated the pathogenic mechanism of the W313G mutation and its role in PEX13 interactions and functions in peroxisome biogenesis. Here, we report for the first time that human PEX13 interacts with itself in peroxisomes in living cells. We demonstrate that the import of PTS1 (peroxisomal targeting signal 1) proteins is specifically disrupted when homooligomerization of PEX13 is interrupted. Live cell FRET microscopy in living cells as well as co-immunoprecipitation experiments reveal that the highly conserved W313 residue is important for self-association of PEX13 but is not required for interaction with PEX14, a well-established interaction partner at the peroxisomal membrane. Experiments with truncated constructs indicate that although the W313G mutation resides in the C-terminal SH3 domain, the N-terminal half is necessary for peroxisomal localization, which in turn appears to be crucial for homooligomerization. Furthermore, rescue of homooligomerization in the W313G mutant cells through complementation with truncation constructs restores import of peroxisomal matrix proteins. Taken together, the thorough analyses of a ZSS patient mutation unraveled the general cell biological function of PEX13 and its mechanism in the import of peroxisomal matrix PTS1 proteins."],["dc.identifier.doi","10.1093/hmg/ddt238"],["dc.identifier.gro","3142277"],["dc.identifier.isi","000325163900003"],["dc.identifier.pmid","23716570"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6498"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0964-6906"],["dc.title","Functional analysis of PEX13 mutation in a Zellweger syndrome spectrum patient reveals novel homooligomerization of PEX13 and its role in human peroxisome biogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","741"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","European Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","748"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Krause, Cindy"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:47:27Z"],["dc.date.available","2017-09-07T11:47:27Z"],["dc.date.issued","2009"],["dc.description.abstract","Zellweger syndrome spectrum (ZSS) comprises a clinically and genetically heterogeneous disease entity, which is caused by mutations in any of the 12 different human PEX genes leading to impaired biogenesis of the peroxisome. Patients potentially suffering from ZSS are diagnosed biochemically by measuring elevated levels of very long chain fatty acids, pristanic acid and phytanic acid in plasma and serum and reduced levels of ether phospholipids in erythrocytes. Published reports on diagnostic procedures for ZSS patients are restricted either to biochemical markers or to defined mutations in a subset of PEX genes. Clarification of the primary genetic defect in an affected patient is crucial for genetic counselling, carrier testing or prenatal diagnosis. In this study, we present a rational diagnostic strategy for patients suspected of ZSS. By combining cell biology and molecular genetic methods in an appropriate sequence, we were able to detect the underlying mutation in various PEX genes within adequate time and cost. We applied this method on 90 patients who presented at our institute, Department of Pediatrics and Pediatric Neurology at Georg August University, and detected 174 mutant alleles within six different PEX genes, including two novel deletions and three new missense mutations in PEX6. Furthermore, this strategy will extend our knowledge on genotype-phenotype correlation in various PEX genes. It will contribute to a better understanding of ZSS pathogenesis, allowing the investigation of the effects of diverse mutations on the interaction between PEX proteins and peroxisomal function in vivo. European Journal of Human Genetics (2009) 17, 741-748; doi: 10.1038/ejhg.2008.252; published online 14 January 2009"],["dc.identifier.doi","10.1038/ejhg.2008.252"],["dc.identifier.gro","3143108"],["dc.identifier.isi","000266289100009"],["dc.identifier.pmid","19142205"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/586"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1018-4813"],["dc.title","Rational diagnostic strategy for Zellweger syndrome spectrum patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]