Rosewich, Hendrik

[["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","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","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.artnumber","7809"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.lastpage","13"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Soliman, Kareem"],["dc.contributor.author","Göttfert, Fabian"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Thoms, Sven"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2019-02-27T10:14:35Z"],["dc.date.available","2019-02-27T10:14:35Z"],["dc.date.issued","2018"],["dc.description.abstract","Peroxisomes are ubiquitous cell organelles involved in many metabolic and signaling functions. Their assembly requires peroxins, encoded by PEX genes. Mutations in PEX genes are the cause of Zellweger Syndrome spectrum (ZSS), a heterogeneous group of peroxisomal biogenesis disorders (PBD). The size and morphological features of peroxisomes are below the diffraction limit of light, which makes them attractive for super-resolution imaging. We applied Stimulated Emission Depletion (STED) microscopy to study the morphology of human peroxisomes and peroxisomal protein localization in human controls and ZSS patients. We defined the peroxisome morphology in healthy skin fibroblasts and the sub-diffraction phenotype of residual peroxisomal structures (‘ghosts’) in ZSS patients that revealed a relation between mutation severity and clinical phenotype. Further, we investigated the 70 kDa peroxisomal membrane protein (PMP70) abundance in relationship to the ZSS sub-diffraction phenotype. This work improves the morphological definition of peroxisomes. It expands current knowledge about peroxisome biogenesis and ZSS pathoethiology to the sub-diffraction phenotype including key peroxins and the characteristics of ghost peroxisomes."],["dc.identifier.doi","10.1038/s41598-018-24119-2"],["dc.identifier.pmid","29773809"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15261"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57637"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/210"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A10: Peroxisomen als modulatorische Einheiten im Herzstoffwechsel und bei Herzinsuffizienz"],["dc.relation.issn","2045-2322"],["dc.relation.workinggroup","RG Thoms (Biochemistry and Molecular Medicine)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Super-resolution imaging reveals the sub-diffraction phenotype of Zellweger Syndrome ghosts and wild-type peroxisomes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"],["local.message.claim","2020-08-07T08:23:16.626+0000|||rp114519|||submit_approve|||dc_contributor_author|||None"]]

[["dc.bibliographiccitation.firstpage","2859"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","2874"],["dc.bibliographiccitation.volume","138"],["dc.contributor.author","Jaffer, Fatima"],["dc.contributor.author","Avbersek, Andreja"],["dc.contributor.author","Vavassori, Rosaria"],["dc.contributor.author","Fons, Carmen"],["dc.contributor.author","Campistol, Jaume"],["dc.contributor.author","Stagnaro, Michela"],["dc.contributor.author","De Grandis, Elisa"],["dc.contributor.author","Veneselli, Edvige"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Gianotta, Melania"],["dc.contributor.author","Zucca, Claudio"],["dc.contributor.author","Ragona, Francesca"],["dc.contributor.author","Granata, Tiziana"],["dc.contributor.author","Nardocci, Nardo"],["dc.contributor.author","Mikati, Mohamed"],["dc.contributor.author","Helseth, Ashley R."],["dc.contributor.author","Boelman, Cyrus"],["dc.contributor.author","Minassian, Berge A."],["dc.contributor.author","Johns, Sophia"],["dc.contributor.author","Garry, Sarah I."],["dc.contributor.author","Scheffer, Ingrid E."],["dc.contributor.author","Gourfinkel-An, Isabelle"],["dc.contributor.author","Carrilho, Ines"],["dc.contributor.author","Aylett, Sarah E."],["dc.contributor.author","Parton, Matthew"],["dc.contributor.author","Hanna, Michael G."],["dc.contributor.author","Houlden, Henry"],["dc.contributor.author","Neville, Brian"],["dc.contributor.author","Kurian, Manju A."],["dc.contributor.author","Novy, Jan"],["dc.contributor.author","Sander, Josemir W."],["dc.contributor.author","Lambiase, Pier D."],["dc.contributor.author","Behr, Elijah R."],["dc.contributor.author","Schyns, Tsveta"],["dc.contributor.author","Arzimanoglou, Alexis"],["dc.contributor.author","Cross, J. Helen"],["dc.contributor.author","Kaski, Juan P."],["dc.contributor.author","Sisodiya, Sanjay M."],["dc.date.accessioned","2018-11-07T09:50:28Z"],["dc.date.available","2018-11-07T09:50:28Z"],["dc.date.issued","2015"],["dc.description.abstract","Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those >= 16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to-electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes. Electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable."],["dc.identifier.doi","10.1093/brain/awv243"],["dc.identifier.isi","000365136200016"],["dc.identifier.pmid","26297560"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12623"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35718"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1460-2156"],["dc.relation.issn","0006-8950"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Therapeutic Advances in Neurological Disorders"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Nessler, Stefan"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2019-08-14T10:39:12Z"],["dc.date.available","2019-08-14T10:39:12Z"],["dc.date.issued","2019"],["dc.description.abstract","Rituximab exerts its clinical efficacy by its specific pattern of depletion of CD20+ B lymphocytes and it has been demonstrated that rituximab is an effective treatment for relapsing remitting multiple sclerosis. X-linked adrenoleukodystrophy (X-ALD), the most common monogenetic neuroinflammatory disorder, shares substantial overlap with multiple sclerosis in the neuropathological changes found in brain tissues in advanced stages of the disease. While there is no effective therapy for these patients, we hypothesized that rituximab might be effective in arresting the neuroinflammatory process. Our detailed clinical, imaging and immunological data revealed that rituximab is not effective in advanced stages of X-ALD and consequently should not be applied for compassionate use in these patients."],["dc.identifier.doi","10.1177/1756286419868133"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16347"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62382"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.publisher","SAGE Publications"],["dc.relation.eissn","1756-2864"],["dc.relation.issn","1756-2864"],["dc.relation.issn","1756-2864"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","B cell depletion can be effective in multiple sclerosis but failed in a patient with advanced childhood cerebral X-linked adrenoleukodystrophy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","347"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Metabolites"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Klemp, Henry Gerd"],["dc.contributor.author","Kettwig, Matthias"],["dc.contributor.author","Streit, Frank"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Krätzner, Ralph"],["dc.date.accessioned","2021-08-12T07:46:01Z"],["dc.date.available","2021-08-12T07:46:01Z"],["dc.date.issued","2021"],["dc.description.abstract","Peroxisomes are central hubs for cell metabolism and their dysfunction is linked to devastating human disorders, such as peroxisomal biogenesis disorders and single peroxisomal enzyme/protein deficiencies. For decades, biochemical diagnostics have been carried out using classical markers such as very long-chain fatty acids (VLCFA), which can be inconspicuous in milder and atypical cases. Holistic metabolomics studies revealed several potentially new biomarkers for peroxisomal disorders for advanced laboratory diagnostics including atypical cases. However, establishing these new markers is a major challenge in routine diagnostic laboratories. We therefore investigated whether the commercially available AbsoluteIDQ p180 kit (Biocrates Lifesciences), which utilizes flow injection and liquid chromatography mass spectrometry, may be used to reproduce some key results from previous global metabolomics studies. We applied it to serum samples from patients with mutations in peroxisomal target genes PEX1, ABCD1, and the HSD17B4 gene. Here we found various changes in sphingomyelins and lysophosphatidylcholines. In conclusion, this kit can be used to carry out extended diagnostics for peroxisomal disorders in routine laboratories, even without access to a metabolomics unit."],["dc.description.abstract","Peroxisomes are central hubs for cell metabolism and their dysfunction is linked to devastating human disorders, such as peroxisomal biogenesis disorders and single peroxisomal enzyme/protein deficiencies. For decades, biochemical diagnostics have been carried out using classical markers such as very long-chain fatty acids (VLCFA), which can be inconspicuous in milder and atypical cases. Holistic metabolomics studies revealed several potentially new biomarkers for peroxisomal disorders for advanced laboratory diagnostics including atypical cases. However, establishing these new markers is a major challenge in routine diagnostic laboratories. We therefore investigated whether the commercially available AbsoluteIDQ p180 kit (Biocrates Lifesciences), which utilizes flow injection and liquid chromatography mass spectrometry, may be used to reproduce some key results from previous global metabolomics studies. We applied it to serum samples from patients with mutations in peroxisomal target genes PEX1, ABCD1, and the HSD17B4 gene. Here we found various changes in sphingomyelins and lysophosphatidylcholines. In conclusion, this kit can be used to carry out extended diagnostics for peroxisomal disorders in routine laboratories, even without access to a metabolomics unit."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3390/metabo11060347"],["dc.identifier.pii","metabo11060347"],["dc.identifier.pmid","34072483"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88599"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/413"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2218-1989"],["dc.relation.orgunit","Klinik für Kinder- und Jugendmedizin"],["dc.relation.workinggroup","RG Gärtner"],["dc.rights","CC BY 4.0"],["dc.title","LC-MS Based Platform Simplifies Access to Metabolomics for Peroxisomal Disorders"],["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","105012"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.volume","143"],["dc.contributor.author","Lazarov, Elinor"],["dc.contributor.author","Hillebrand, Merle"],["dc.contributor.author","Schröder, Simone"],["dc.contributor.author","Ternka, Katharina"],["dc.contributor.author","Hofhuis, Julia"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Barrantes-Freer, Alonso"],["dc.contributor.author","Pardo, Luis A."],["dc.contributor.author","Fruergaard, Marlene U."],["dc.contributor.author","Nissen, Poul"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Rosewich, Hendrik"],["dc.date.accessioned","2021-04-14T08:23:22Z"],["dc.date.available","2021-04-14T08:23:22Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.nbd.2020.105012"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17488"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80889"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","0969-9961"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Comparative analysis of alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism ATP1A3 mutations reveals functional deficits, which do not correlate with disease severity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","109"],["dc.bibliographiccitation.journal","BMC Medical Genetics"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Thoms, Sven"],["dc.contributor.author","Gronborg, Sabine"],["dc.contributor.author","Rabenau, Jana"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:43:26Z"],["dc.date.available","2017-09-07T11:43:26Z"],["dc.date.issued","2011"],["dc.description.abstract","Background: Mutations in PEX1 are the most common primary cause of Zellweger syndrome. In addition to exonic mutations, deletions and splice site mutations two 5' polymorphisms at c.-137 and c.-53 with a potential influence on PEX1 protein levels have been described in the 5' untranslated region (UTR) of the PEX1 gene. Methods: We used RACE and in silico promoter prediction analysis to study the 5' UTR of PEX1. We determined the distribution of PEX1 5' polymorphisms in a cohort of 30 Zellweger syndrome patients by standard DNA sequencing. 5' polymorphisms were analysed in relation to the two most common mutations in PEX1 and were incorporated into a novel genotype-phenotype analysis by correlation of three classes of PEX1 mutations with patient survival. Results: We provide evidence that the polymorphism 137 bp upstream of the ATG codon is not part of the UTR, rendering it a promoter polymorphism. We show that the first, but not the second most common PEX1 mutation arose independently of a specific upstream polymorphic constellation. By genotype-phenotype analysis we identified patients with identical exonic mutation and identical 5' polymorphisms, but strongly differing survival. Conclusions: Our study suggests that two different types of PEX1 5' polymorphisms have to be distinguished: a 5' UTR polymorphism at position c.-53 and a promoter polymorphism 137 bp upstream of the PEX1 start codon. Our results indicate that the exonic PEX1 mutation correlates with patient survival, but the two 5' polymorphisms analysed in this study do not have to be considered for diagnostic and/or prognostic purposes."],["dc.identifier.doi","10.1186/1471-2350-12-109"],["dc.identifier.gro","3142685"],["dc.identifier.isi","000294566100001"],["dc.identifier.pmid","21846392"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6929"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: BMBF (German LEUKONET); Deutsche Forschungsgemeinschaft [GA354/7-1]"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2350"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Characterization of two common 5 ' polymorphisms in PEX1 and correlation to survival in PEX1 peroxisome biogenesis disorder patients"],["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"],["local.message.claim","2020-08-07T08:23:16.626+0000|||rp114519|||submit_approve|||dc_contributor_author|||None"]]