Gärtner, Jutta

[["dc.bibliographiccitation.artnumber","2123"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Wrede, Arne"],["dc.contributor.author","Schweizer, Michaela"],["dc.contributor.author","Huewel, Sabine"],["dc.contributor.author","Galla, Hans-Joachim"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Bueckers, Johanna"],["dc.contributor.author","Low, Philip S."],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Steinfeld, Robert"],["dc.date.accessioned","2017-09-07T11:47:39Z"],["dc.date.available","2017-09-07T11:47:39Z"],["dc.date.issued","2013"],["dc.description.abstract","Loss of folate receptor-alpha function is associated with cerebral folate transport deficiency and childhood-onset neurodegeneration. To clarify the mechanism of cerebral folate transport at the blood-cerebrospinal fluid barrier, we investigate the transport of 5-methyltetrahydrofolate in polarized cells. Here we identify folate receptor-alpha-positive intralumenal vesicles within multivesicular bodies and demonstrate the directional cotransport of human folate receptor-alpha, and labelled folate from the basolateral to the apical membrane in rat choroid plexus cells. Both the apical medium of folate receptor-alpha-transfected rat choroid plexus cells and human cerebrospinal fluid contain folate receptor-alpha-positive exosomes. Loss of folate receptor-alpha-expressing cerebrospinal fluid exosomes correlates with severely reduced 5-methyltetrahydrofolate concentration, corroborating the importance of the folate receptor-alpha-mediated folate transport in the cerebrospinal fluid. Intraventricular injections of folate receptor-alpha-positive and -negative exosomes into mouse brains demonstrate folate receptor-alpha-dependent delivery of exosomes into the brain parenchyma. Our results unravel a new pathway of folate receptor-alpha-dependent exosome-mediated folate delivery into the brain parenchyma and opens new avenues for cerebral drug targeting."],["dc.identifier.doi","10.1038/ncomms3123"],["dc.identifier.gro","3142330"],["dc.identifier.isi","000323715900003"],["dc.identifier.pmid","23828504"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9774"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7086"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-1723"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","submitted_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","74"],["dc.bibliographiccitation.journal","BMC Neurology"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Kettwig, Matthias"],["dc.contributor.author","Elpeleg, Orly"],["dc.contributor.author","Wegener, Eike"],["dc.contributor.author","Dreha-Kulaczewski, Steffi F."],["dc.contributor.author","Henneke, Marco"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Huppke, Peter"],["dc.date.accessioned","2017-09-07T11:44:54Z"],["dc.date.available","2017-09-07T11:44:54Z"],["dc.date.issued","2016"],["dc.description.abstract","Background: Mutations in proteins involved in the glycosylphosphatidylinositol anchor biosynthesis and remodeling pathway are associated with autosomal recessive forms of intellectual disability. Recently mutations in the PGAP1 gene that codes for PGAP1, a protein localized in the endoplasmic reticulum responsible for the first step of the remodeling of glycosylphosphatidylinositol was linked to a disorder characterized by psychomotor retardation and facial dysmorphism. Whole exome sequencing (WES) was performed in siblings with severely delayed myelination and psychomotor retardation. Mutations in PGAP1 were confirmed by Sanger sequencing and RNA analysis. A literature search was performed to describe the emerging phenotype of PGAP1 related disease. Case presentation: WES resulted in the detection of two novel compound heterozygous mutations in PGAP1, one base pair insertion leading to a frame shift c.334_335InsA (p.A112fs) and a splice site mutation leading to exon skipping c.G1173C (p.L391L). A symptom not described in PGAP1 related disorder before but prominent in the siblings were recurrent apnea especially during sleep that persisted at least until age 2 years. Sequential cerebral MRI at age one and two year(s) respectively revealed frontal accentuated brain atrophy and significantly delayed myelination. Conclusion: We report siblings with two novel mutations in PGAP1. Other that the common symptoms related to PGAP1 mutations including non-progressive psychomotor retardation, neonatal feeding problems, microcephaly and brain atrophy these patients displayed severely delayed myelination and recurrent apneas thereby widing the clinical spectrum associated with such mutations."],["dc.identifier.doi","10.1186/s12883-016-0602-7"],["dc.identifier.gro","3141684"],["dc.identifier.isi","000376577000003"],["dc.identifier.pmid","27206732"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13279"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8872"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2377"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Compound heterozygous variants in PGAP1 causing severe psychomotor retardation, brain atrophy, recurrent apneas and delayed myelination: a case report and literature review"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","145"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Inherited Metabolic Disease"],["dc.bibliographiccitation.lastpage","155"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","Schiller, Stina"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Grünewald, Stephanie"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2021-04-14T08:27:49Z"],["dc.date.available","2021-04-14T08:27:49Z"],["dc.date.issued","2019"],["dc.description.abstract","Abstract The development and organisation of the human brain start in the embryonic stage and is a highly complex orchestrated process. It depends on series of cellular mechanisms that are precisely regulated by multiple proteins, signalling pathways and non‐protein‐coding genes. A crucial process during cerebral cortex development is the migration of nascent neuronal cells to their appropriate positions and their associated differentiation into layer‐specific neurons. Neuronal migration defects (NMD) comprise a heterogeneous group of neurodevelopmental disorders including monogenetic disorders and residual syndromes due to damaging factors during prenatal development like infections, maternal diabetes mellitus or phenylketonuria, trauma, and drug use. Multifactorial causes are also possible. Classification into lissencephaly, polymicrogyria, schizencephaly, and neuronal heterotopia is based on the visible morphologic cortex anomalies. Characteristic clinical features of NMDs are severe psychomotor developmental delay, severe intellectual disability, intractable epilepsy, and dysmorphisms. Neurometabolic disorders only form a small subgroup within the large group of NMDs. The prototypes are peroxisomal biogenesis disorders, peroxisomal ß‐oxidation defects and congenital disorders of O‐glycosylation. The rapid evolution of biotechnology has resulted in an ongoing identification of metabolic and non‐metabolic disease genes for NMDs. Nevertheless, we are far away from understanding the specific role of cortical genes and metabolites on spatial and temporal regulation of human cortex development and associated malformations. This limited understanding of the pathogenesis hinders the attempt for therapeutic approaches. In this article, we provide an overview of the most important cortical malformations and potential underlying neurometabolic disorders."],["dc.identifier.doi","10.1002/jimd.12194"],["dc.identifier.eissn","1573-2665"],["dc.identifier.issn","0141-8955"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82413"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","John Wiley \\u0026 Sons, Inc."],["dc.relation.eissn","1573-2665"],["dc.relation.issn","0141-8955"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Inborn errors of metabolism leading to neuronal migration defects"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","673"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","674"],["dc.bibliographiccitation.volume","138"],["dc.contributor.author","Stumpf, Sina K."],["dc.contributor.author","Berghoff, Stefan A."],["dc.contributor.author","Trevisiol, Andrea"],["dc.contributor.author","Spieth, Lena"],["dc.contributor.author","Düking, Tim"],["dc.contributor.author","Schneider, Lennart V."],["dc.contributor.author","Schlaphoff, Lennart"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Bley, Annette"],["dc.contributor.author","Burfeind, Dinah"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Mitkovski, Miso"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Guder, Philipp"],["dc.contributor.author","Röhse, Heiko"],["dc.contributor.author","Denecke, Jonas"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Saher, Gesine"],["dc.date.accessioned","2019-11-04T14:10:22Z"],["dc.date.accessioned","2021-10-27T13:21:24Z"],["dc.date.available","2019-11-04T14:10:22Z"],["dc.date.available","2021-10-27T13:21:24Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s00401-019-02064-2"],["dc.identifier.pmid","31482207"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16592"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92019"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1432-0533"],["dc.relation.iserratumof","/handle/2/62293"],["dc.relation.issn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Correction to: Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus–Merzbacher disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","erratum_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","6530"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Kettwig, Matthias"],["dc.contributor.author","Ternka, Katharina"],["dc.contributor.author","Wendland, Kristin"],["dc.contributor.author","Krüger, Dennis Manfred"],["dc.contributor.author","Zampar, Silvia"],["dc.contributor.author","Schob, Charlotte"],["dc.contributor.author","Franz, Jonas"],["dc.contributor.author","Aich, Abhishek"],["dc.contributor.author","Winkler, Anne"],["dc.contributor.author","Sakib, M. Sadman"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2021-12-01T09:23:01Z"],["dc.date.available","2021-12-01T09:23:01Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Infantile-onset RNaseT2 deficient leukoencephalopathy is characterised by cystic brain lesions, multifocal white matter alterations, cerebral atrophy, and severe psychomotor impairment. The phenotype is similar to congenital cytomegalovirus brain infection and overlaps with type I interferonopathies, suggesting a role for innate immunity in its pathophysiology. To date, pathophysiological studies have been hindered by the lack of mouse models recapitulating the neuroinflammatory encephalopathy found in patients. In this study, we generated Rnaset2 −/− mice using CRISPR/Cas9-mediated genome editing. Rnaset2 −/− mice demonstrate upregulation of interferon-stimulated genes and concurrent IFNAR1-dependent neuroinflammation, with infiltration of CD8 + effector memory T cells and inflammatory monocytes into the grey and white matter. Single nuclei RNA sequencing reveals homeostatic dysfunctions in glial cells and neurons and provide important insights into the mechanisms of hippocampal-accentuated brain atrophy and cognitive impairment. The Rnaset2 −/− mice may allow the study of CNS damage associated with RNaseT2 deficiency and may be used for the investigation of potential therapies."],["dc.identifier.doi","10.1038/s41467-021-26880-x"],["dc.identifier.pii","26880"],["dc.identifier.pmid","34764281"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94539"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/361"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/48"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/141"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B06: Die Rolle von RNA in Synapsenphysiologie und Neurodegeneration"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)"],["dc.relation.workinggroup","RG Gärtner"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.rights","CC BY 4.0"],["dc.title","Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1174"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Inherited Metabolic Disease"],["dc.bibliographiccitation.lastpage","1185"],["dc.bibliographiccitation.volume","44"],["dc.contributor.affiliation","Klemp, Henry; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Nessler, Stefan; 2\r\nInstitute of Neuropathology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Streit, Frank; 3\r\nInstitute for Clinical Chemistry, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Krätzner, Ralph; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Rosewich, Hendrik; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.affiliation","Gärtner, Jutta; 1\r\nDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen\r\nGeorg August University\r\nGöttingen Germany"],["dc.contributor.author","Kettwig, Matthias"],["dc.contributor.author","Klemp, Henry"],["dc.contributor.author","Nessler, Stefan"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Krätzner, Ralph"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2021-06-01T09:42:02Z"],["dc.date.available","2021-06-01T09:42:02Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T01:43:41Z"],["dc.description.abstract","Abstract X‐linked adrenoleukodystrophy (X‐ALD) is the most common leukodystrophy. Despite intensive research in recent years, it remains unclear, what drives the different clinical disease courses. Due to this missing pathophysiological link, therapy for the childhood cerebral disease course of X‐ALD (CCALD) remains symptomatic; the allogenic hematopoietic stem cell transplantation or hematopoietic stem‐cell gene therapy is an option for early disease stages. The inclusion of dried blood spot (DBS) C26:0‐lysophosphatidylcholine to newborn screening in an increasing number of countries is leading to an increasing number of X‐ALD patients diagnosed at risk for CCALD. Current follow‐up in asymptomatic boys with X‐ALD requires repetitive cerebral MRIs under sedation. A reliable and easily accessible biomarker that predicts CCALD would therefore be of great value. Here we report the application of targeted metabolomics by AbsoluteIDQ p180‐Kit from Biocrates to search for suitable biomarkers in X‐ALD. LysoPC a C20:3 and lysoPC a C20:4 were identified as metabolites that indicate neuroinflammation after induction of experimental autoimmune encephalitis in the serum of Abcd1tm1Kds mice. Analysis of serum from X‐ALD patients also revealed different concentrations of these lipids at different disease stages. Further studies in a larger cohort of X‐ALD patient sera are needed to prove the diagnostic value of these lipids for use as early biomarkers for neuroinflammation in CCALD patients."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","Niedersächsisches Ministerium für Wissenschaft und Kultur http://dx.doi.org/10.13039/501100010570"],["dc.description.sponsorship","Germany's Excellence Strategy"],["dc.description.sponsorship","Transregional Collaborative Research Center"],["dc.identifier.doi","10.1002/jimd.12389"],["dc.identifier.pmid","33855724"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85119"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/270"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1573-2665"],["dc.relation.issn","0141-8955"],["dc.relation.workinggroup","RG Gärtner"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes."],["dc.title","Targeted metabolomics revealed changes in phospholipids during the development of neuroinflammation in Abcd1 tm1Kds mice and X‐linked adrenoleukodystrophy patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1321"],["dc.bibliographiccitation.journal","Acta Crystallographica Section D Biological Crystallography"],["dc.bibliographiccitation.lastpage","1335"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Sidhu, Navdeep S."],["dc.contributor.author","Schreiber, Kathrin"],["dc.contributor.author","Proepper, Kevin"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Uson, Isabel"],["dc.contributor.author","Sheldrick, George M."],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Steinfeld, Robert"],["dc.date.accessioned","2017-09-07T11:46:15Z"],["dc.date.available","2017-09-07T11:46:15Z"],["dc.date.issued","2014"],["dc.description.abstract","Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 A resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder."],["dc.identifier.doi","10.1107/S1399004714002739"],["dc.identifier.gro","3142131"],["dc.identifier.isi","000335952500014"],["dc.identifier.pmid","24816101"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12116"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4888"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1399-0047"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","92"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Blood Purification"],["dc.bibliographiccitation.lastpage","97"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Koziolek, Michael J."],["dc.contributor.author","Friede, Tim"],["dc.contributor.author","Ellenberger, David"],["dc.contributor.author","Sigler, Matthias"],["dc.contributor.author","Huppke, Brenda"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Mueller, Gerhard-Anton"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Mühlhausen, Johannes"],["dc.date.accessioned","2017-09-07T11:48:19Z"],["dc.date.available","2017-09-07T11:48:19Z"],["dc.date.issued","2013"],["dc.description.abstract","Background/Aims: In adults, plasma exchange (PE) has been shown to be an efficient treatment for severe relapses of acute inflammatory CNS demyelinating diseases. The aim of this study was to evaluate the safety and efficacy of this treatment in pediatric patients. Methods: We retrospectively analyzed a single-center cohort of pediatric patients with inflammatory CNS demyelinating disorders who underwent apheresis between 2007 and 2011. Results: Ten patients (mean age: 11.6 +/- 3.4 years) with an acute relapse of multiple sclerosis (n = 5), neuromyelitis optica (n = 2) or acute disseminated encephalomyelitis were included. All received methylprednisolone prior to treatment with either PE (n = 5) or immunoadsorption (n = 5). Apheresis-related side effects were either self-limiting or easily managed. EDSS (Expanded Disability Status Scale) improved in 7 of 8 patients during apheresis and in all patients within 30 days from a median of 7.5 to 1 (p < 0.01). The visual acuity initially worsened during the procedure in 3 of 7 affected eyes (mean 0.09), but improved in all at follow-up (mean: 0.5; p = 0.008). Conclusions: Apheresis was well tolerated and associated with a favorable outcome in all pediatric patients similar to reports in adults. Copyright (C) 2013 S. Karger AG, Basel"],["dc.identifier.doi","10.1159/000354077"],["dc.identifier.gro","3142409"],["dc.identifier.isi","000328188600005"],["dc.identifier.pmid","24021839"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10815"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7963"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","S. Karger AG"],["dc.relation.eissn","1421-9735"],["dc.relation.issn","0253-5068"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Therapeutic Apheresis in Pediatric Patients with Acute CNS Inflammatory Demyelinating Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","764"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","The Lancet Neurology"],["dc.bibliographiccitation.lastpage","773"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Maschke, Ulrike"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Frommolt, Peter"],["dc.contributor.author","Zim, Birgit"],["dc.contributor.author","Ebinger, Friedrich"],["dc.contributor.author","Siemes, Hartmut"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:48:26Z"],["dc.date.available","2017-09-07T11:48:26Z"],["dc.date.issued","2012"],["dc.description.abstract","Background Alternating hemiplegia of childhood (AHC) is a rare neurological disorder characterised by early-onset episodes of hemiplegia, dystonia, various paroxysmal symptoms, and developmental impairment. Almost all cases of AHC are sporadic but AHC concordance in monozygotic twins and dominant transmission in a family with a milder phenotype have been reported. Thus, we aimed to identify de-novo mutations associated with this disease. Methods We recruited patients with clinically characterised AHC from paediatric neurology departments in Germany and with the aid of a parental support group between Sept, 2004, and May 18, 2012. We used whole-exome sequencing of three proband-parent trios to identify a disease-associated gene and then tested whether mutations in the gene were also present in the remaining patients and their healthy parents. We analysed genotypes and characterised their associations with the phenotypic spectrum of the disease. Findings We studied 15 female and nine male patients with AHC who were aged 8-35 years. ATP1A3 emerged as the disease-associated gene in AHC. Whole-exome sequencing showed three heterozygous de-novo missense mutations. Sequencing of the 21 remaining affected individuals identified disease-associated mutations in ATP1A3 in all patients, including six de-novo missense mutations and one de-novo splice-site mutation. Because ATP1A3 is also the gene associated with rapid-onset dystonia-parkinsonism (DYT12, OMIM 128235) we compared the genotypes and phenotypes of patients with AHC in our cohort with those of patients with rapid-onset dystonia-parkinsonism reported in the scientific literature. We noted overlapping clinical features, such as abrupt onset of dystonic episodes often triggered by emotional stress, a rostrocaudal (face to arm to leg) gradient of involvement, and signs of brainstem dysfunction, as well as clearly differentiating clinical characteristics, such as episodic hemiplegia and quadriplegia. Interpretation Mutation analysis of the ATP1A3 gene in patients who met clinical criteria for AHC allows for definite genetic diagnosis and sound genetic counselling. AHC and rapid-onset dystonia-parkinsonism are allelic diseases related to mutations in ATP1A3 and form a phenotypical continuum of a dystonic movement disorder."],["dc.identifier.doi","10.1016/S1474-4422(12)70182-5"],["dc.identifier.gro","3142472"],["dc.identifier.isi","000307911700011"],["dc.identifier.pmid","22850527"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11305"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8662"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Eva Luise and Horst Kohler Foundation for Humans with Rare Diseases"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Inc"],["dc.relation.eissn","1474-4465"],["dc.relation.issn","1474-4422"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","389"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Molecular Medicine"],["dc.bibliographiccitation.lastpage","398"],["dc.bibliographiccitation.volume","89"],["dc.contributor.author","Brendel, Cornelia"],["dc.contributor.author","Belakhov, Valery"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Wegener, Eike"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Nudelman, Igor"],["dc.contributor.author","Baasov, Timor"],["dc.contributor.author","Huppke, Peter"],["dc.date.accessioned","2017-09-07T11:44:20Z"],["dc.date.available","2017-09-07T11:44:20Z"],["dc.date.issued","2011"],["dc.description.abstract","Thirty-five percent of patients with Rett syndrome carry nonsense mutations in the MECP2 gene. We have recently shown in transfected HeLa cells that readthrough of nonsense mutations in the MECP2 gene can be achieved by treatment with gentamicin and geneticin. This study was performed to test if readthrough can also be achieved in cells endogenously expressing mutant MeCP2 and to evaluate potentially more effective readthrough compounds. A mouse model was generated carrying the R168X mutation in the MECP2 gene. Transfected HeLa cells expressing mutated MeCP2 fusion proteins and mouse ear fibroblasts isolated from the new mouse model were treated with gentamicin and the novel aminoglycosides NB30, NB54, and NB84. The localization of the readthrough product was tested by immunofluorescence. Read-through of the R168X mutation in mouse ear fibroblasts using gentamicin was detected but at lower level than in HeLa cells. As expected, the readthrough product, full-length Mecp2 protein, was located in the nucleus. NB54 and NB84 induced readthrough more effectively than gentamicin, while NB30 was less effective. Readthrough of nonsense mutations can be achieved not only in transfected HeLa cells but also in fibroblasts of the newly generated Mecp2(R168X) mouse model. NB54 and NB84 were more effective than gentamicin and are therefore promising candidates for readthrough therapy in Rett syndrome patients."],["dc.identifier.doi","10.1007/s00109-010-0704-4"],["dc.identifier.gro","3142749"],["dc.identifier.isi","000289689200007"],["dc.identifier.pmid","21120444"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6593"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/187"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.relation.issn","0946-2716"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]