Krätzner, Ralph

[["dc.bibliographiccitation.firstpage","2100"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","European Journal of Organic Chemistry"],["dc.bibliographiccitation.lastpage","2106"],["dc.contributor.author","Pitulescu, Marian"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Knepel, Willhart"],["dc.contributor.author","Diederichsen, Ulf"],["dc.date.accessioned","2018-11-07T11:16:29Z"],["dc.date.available","2018-11-07T11:16:29Z"],["dc.date.issued","2008"],["dc.description.abstract","Two formacetal-linked dinucleotides TT and TT were synthesized as phosphoramidite building blocks for solid-phase synthesis. Incorporated in a 29-mer DNA, the oligomers P3(TT) and P3(TA) were studied with respect to the binding activity towards the Pax6 homeodomain. Substitution of the negatively charged phosphodiester by a neutral formacetal linker facilitates the bent conformation of double-stranded DNA. The duplex stability was affected more significantly by the TT formacetal modification, whereas destabilization induced by TA was less pronounced. Based on CD spectroscopy, the TA formacetal-modified oligomer P3(TA) A has mainly B-DNA topology, whereas the P3(TT) modified oligomet significantly deviated from B-form DNA. The binding affinity of the P3 oligomer towards Pax6 HD was investigated by in vitro EMSA experiments providing even a small increase in binding affinity for the P3(TA) T oligomer. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)."],["dc.identifier.doi","10.1002/ejoc.200701178"],["dc.identifier.isi","000255508600010"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54599"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1434-193X"],["dc.title","Synthesis of formacetal-linked dinucleotides to facilitate dsDNA bending and binding to the homeodomain of Pax6"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","515"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.lastpage","525"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Knoell, Ralph"],["dc.contributor.author","Postel, Ruben"],["dc.contributor.author","Wang, Jianming"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Hennecke, Gerrit"],["dc.contributor.author","Vacaru, Andrei M."],["dc.contributor.author","Vakeel, Padmanabhan"],["dc.contributor.author","Schubert, Cornelia"],["dc.contributor.author","Murthy, Kenton"],["dc.contributor.author","Rana, Brinda K."],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Knoell, Gudrun"],["dc.contributor.author","Schaefer, Katrin"],["dc.contributor.author","Hayashi, Takeharu"],["dc.contributor.author","Holm, Torbjorn"],["dc.contributor.author","Kimura, Akinori"],["dc.contributor.author","Schork, Nicholas"],["dc.contributor.author","Toliat, Mohammad Reza"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Schultheiss, Heinz-Peter"],["dc.contributor.author","Schaper, Wolfgang"],["dc.contributor.author","Schaper, Jutta"],["dc.contributor.author","Bos, Erik"],["dc.contributor.author","Hertog, Jeroen den"],["dc.contributor.author","van Eeden, Fredericus J. M."],["dc.contributor.author","Peters, Peter J."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Chien, Kenneth R."],["dc.contributor.author","Bakkers, Jeroen"],["dc.date.accessioned","2017-09-07T11:49:27Z"],["dc.date.available","2017-09-07T11:49:27Z"],["dc.date.issued","2007"],["dc.description.abstract","Background - Extracellular matrix proteins, such as laminins, and endothelial cells are known to influence cardiomyocyte performance; however, the underlying molecular mechanisms remain poorly understood. Methods and Results - We used a forward genetic screen in zebrafish to identify novel genes required for myocardial function and were able to identify the lost-contact (loc) mutant, which encodes a nonsense mutation in the integrin-linked kinase ( ilk) gene. This loc/ilk mutant is associated with a severe defect in cardiomyocytes and endothelial cells that leads to severe myocardial dysfunction. Additional experiments revealed the epistatic regulation between laminin-alpha 4 (Lama4), integrin, and Ilk, which led us to screen for mutations in the human ILK and LAMA4 genes in patients with severe dilated cardiomyopathy. We identified 2 novel amino acid residue - altering mutations (2828C > T [Pro943Leu] and 3217C > T [Arg1073X]) in the integrin-interacting domain of the LAMA4 gene and 1 mutation (785C > T [Ala262Val]) in the ILK gene. Biacore quantitative protein/protein interaction data, which have been used to determine the equilibrium dissociation constants, point to the loss of integrin-binding capacity in case of the Pro943Leu (K-d = 5 +/- 3 mu mol/L) and Arg1073X LAMA4 (K-d=1 +/- 0.2 mu mol/L) mutants compared with the wild-type LAMA4 protein (K-d=440 +/- 20nmol/L). Additional functional data point to the loss of endothelial cells in affected patients as a direct consequence of the mutant genes, which ultimately leads to heart failure. Conclusions - This is the first report on mutations in the laminin, integrin, and ILK system in human cardiomyopathy, which has consequences for endothelial cells as well as for cardiomyocytes, thus providing a new genetic basis for dilated cardiomyopathy in humans."],["dc.identifier.doi","10.1161/CIRCULATIONAHA.107.689984"],["dc.identifier.gro","3143464"],["dc.identifier.isi","000248456000009"],["dc.identifier.pmid","17646580"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/981"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0009-7322"],["dc.title","Laminin-alpha 4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.volume","375"],["dc.contributor.author","Oetjen, Elke"],["dc.contributor.author","Blume, Roland"],["dc.contributor.author","Cierny, I."],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Stein, R."],["dc.contributor.author","Knepel, Willhart"],["dc.date.accessioned","2018-11-07T11:04:44Z"],["dc.date.available","2018-11-07T11:04:44Z"],["dc.date.issued","2007"],["dc.format.extent","49"],["dc.identifier.isi","000245997000216"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51901"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","48th Spring Meeting of the Deutsche-Gesellschaft-fur Experimentelle-ung-Klinische-Pharmakologie-und-Toxikologie"],["dc.relation.eventlocation","Mainz, GERMANY"],["dc.relation.issn","0028-1298"],["dc.title","Inhibition of MafA transcriptional activity contributes to the inhibition of human insulin gene transcription by MEKK1 and interleukin-1beta"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","1255"],["dc.bibliographiccitation.journal","ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY"],["dc.bibliographiccitation.lastpage","1262"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Kratzner, R."],["dc.contributor.author","Debreczeni, J. E."],["dc.contributor.author","Pape, T."],["dc.contributor.author","Schneider, Thomas R."],["dc.contributor.author","Wentzel, A."],["dc.contributor.author","Kolmar, Harald"],["dc.contributor.author","Sheldrick, George M."],["dc.contributor.author","Uson, I."],["dc.date.accessioned","2018-11-07T10:55:49Z"],["dc.date.available","2018-11-07T10:55:49Z"],["dc.date.issued","2005"],["dc.description.abstract","The Ecballium elaterium trypsin inhibitor II (EETI-II) belongs to the family of squash inhibitors and is one of the strongest inhibitors known for trypsin. The eight independent molecules of EETI-II in the crystal structure reported here provide a good opportunity to test the hypothesis that this small cystine-knot protein (knottin) is sufficiently rigid to be used as a molecular scaffold for protein-engineering purposes. To extend this test, the structures of two complexes of EETI-II with trypsin have also been determined, one carrying a four-amino-acid mutation of EETI-II. The remarkable similarity of these structures confirms the rigidity of the molecular framework and hence its suitability as a molecular scaffold."],["dc.identifier.doi","10.1107/S0907444905021207"],["dc.identifier.isi","000231243400011"],["dc.identifier.pmid","16131759"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49872"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0907-4449"],["dc.title","Structure of Ecballium elaterium trypsin inhibitor II (EETI-II): a rigid molecular scaffold"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","56"],["dc.bibliographiccitation.journal","Genome Medicine"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Seitz, Tina"],["dc.contributor.author","Stalmann, Robert"],["dc.contributor.author","Dalila, Nawar"],["dc.contributor.author","Chen, Jiayin"],["dc.contributor.author","Pojar, Sherin"],["dc.contributor.author","Pereira, Joao N. dos Santos"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Brockmoeller, Juergen"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.date.accessioned","2018-11-07T09:55:48Z"],["dc.date.available","2018-11-07T09:55:48Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: The organic cation transporter OCT1 (SLC22A1) mediates the uptake of vitamin B1, cationic drugs, and xenobiotics into hepatocytes. Nine percent of Caucasians lack or have very low OCT1 activity due to loss-of-function polymorphisms in OCT1 gene. Here we analyzed the global genetic variability in OCT1 to estimate the therapeutic relevance of OCT1 polymorphisms in populations beyond Caucasians and to identify evolutionary patterns of the common loss of OCT1 activity in humans. Methods: We applied massively parallel sequencing to screen for coding polymorphisms in 1,079 unrelated individuals from 53 populations worldwide. The obtained data was combined with the existing 1000 Genomes data comprising an additional 1,092 individuals from 14 populations. The identified OCT1 variants were characterized in vitro regarding their cellular localization and their ability to transport 10 known OCT1 substrates. Both the population genetics data and transport data were used in tandem to generate a world map of loss of OCT1 activity. Results: We identified 16 amino acid substitutions potentially causing loss of OCT1 function and analyzed them together with five amino acid substitutions that were not expected to affect OCT1 function. The variants constituted 16 major alleles and 14 sub-alleles. Six major alleles showed improper subcellular localization leading to substrate-wide loss in activity. Five major alleles showed correct subcellular localization, but substrate-specific loss of activity. Striking differences were observed in the frequency of loss of OCT1 activity worldwide. While most East Asian and Oceanian individuals had completely functional OCT1, 80 % of native South American Indians lacked functional OCT1 alleles. In East Asia and Oceania the average nucleotide diversity of the loss-of-function variants was much lower than that of the variants that do not affect OCT1 function (ratio of 0.03) and was significantly lower than the theoretically expected heterozygosity (Tajima's D=-1.64, P < 0.01). Conclusions: Comprehensive genetic analyses showed strong global variations in the frequency of loss of OCT1 activity with selection pressure for maintaining OCT1 activity in East Asia and Oceania. These results not only enable pharmacogenetically-based optimization of drug treatment worldwide, but may help elucidate the functional role of human OCT1."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2015"],["dc.identifier.doi","10.1186/s13073-015-0172-0"],["dc.identifier.isi","000357566500001"],["dc.identifier.pmid","26157489"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13466"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36829"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1756-994X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Global genetic analyses reveal strong inter-ethnic variability in the loss of activity of the organic cation transporter OCT1"],["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.firstpage","2125"],["dc.bibliographiccitation.journal","ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY"],["dc.bibliographiccitation.lastpage","2132"],["dc.bibliographiccitation.volume","59"],["dc.contributor.author","Debreczeni, J. E."],["dc.contributor.author","Girmann, B."],["dc.contributor.author","Zeeck, Axel"],["dc.contributor.author","Kratzner, R."],["dc.contributor.author","Sheldrick, George M."],["dc.date.accessioned","2018-11-07T10:34:08Z"],["dc.date.available","2018-11-07T10:34:08Z"],["dc.date.issued","2003"],["dc.description.abstract","The crystal structure of viscotoxin A3 (VT A3) extracted from European mistletoe ( Viscum album L.) has been solved using the anomalous diffraction of the native S atoms measured in-house with Cu Kalpha radiation to a resolution of 2.2 Angstrom and truncated to 2.5 Angstrom. A 1.75 Angstrom resolution synchrotron data set was used for phase expansion and refinement. An innovation in the dual-space substructure-solution program SHELXD enabled the individual S atoms of the disulfide bonds to be located using the Cu Kalpha data; this resulted in a marked improvement in the phasing compared with the use of super-S atoms. The VT A3 monomer consists of 46 amino acids with three disulfide bridges and has an overall fold resembling the canonical architecture of the alpha- and beta-thionins, a capital letter L. The asymmetric unit consists of two monomers related by a local twofold axis and held together by hydrophobic interactions between the monomer units. One phosphate anion (confirmed by P-31-NMR and MS) is associated with each monomer."],["dc.identifier.doi","10.1107/S0907444903018973"],["dc.identifier.isi","000186884000010"],["dc.identifier.pmid","14646070"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44789"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Munksgaard"],["dc.relation.issn","0907-4449"],["dc.title","Structure of viscotoxin A3: disulfide location from weak SAD data"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","2803"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part A"],["dc.bibliographiccitation.lastpage","2807"],["dc.bibliographiccitation.volume","173"],["dc.contributor.author","Weissbach, Susann"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Krätzner, Ralph"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Rosenbaum, Thorsten"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2018-04-23T11:47:26Z"],["dc.date.available","2018-04-23T11:47:26Z"],["dc.date.issued","2017"],["dc.description.abstract","Cabezas type of X‐linked syndromic intellectual disability (MRXSC; MIM300354) is a rare X‐linked recessive intellectual disability characterized primarily by intellectual disability, short stature, hypogonadism, and gait abnormalities. It is caused by a wide spectrum of hemizygous variants in CUL4B. In a 10‐year‐old boy with an exceptional leukoencephalopathy pattern, we identified a new missense variant p.Leu329Gln in CUL4B using “Mendeliome” sequencing. However, his phenotype does not include the severe characteristics currently known for MRXSC. We discuss the divergent phenotype and propose a potential connection between the different CUL4B variants and corresponding phenotypes in the context of the current literature as well as 3D homology modeling."],["dc.identifier.doi","10.1002/ajmg.a.38390"],["dc.identifier.gro","3142217"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13339"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","1552-4825"],["dc.title","A new CUL4B variant associated with a mild phenotype and an exceptional pattern of leukoencephalopathy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2845"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics"],["dc.bibliographiccitation.lastpage","2849"],["dc.bibliographiccitation.volume","152A"],["dc.contributor.author","Gronborg, Sabine"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Spiegler, Juliane"],["dc.contributor.author","Ferdinandusse, Sacha"],["dc.contributor.author","Wanders, Ronald J. A."],["dc.contributor.author","Waterham, Hans R."],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:45:12Z"],["dc.date.available","2017-09-07T11:45:12Z"],["dc.date.issued","2010"],["dc.description.abstract","D-bifunctional protein deficiency (DBPD) is an autosomal recessive disease caused by a defect in peroxisomal beta-oxidation. The majority of patients suffer from a severe neurological disease with neonatal hypotonia and seizures and die within the first 2 years of life. Few patients show milder clinical phenotypes with prolonged survival. The diagnosis relies on the clinical presentation, measurement of peroxisomal markers, including very long chain fatty acids (VLCFA) in plasma, followed by enzymatic studies in fibroblasts and genetic testing. Diagnosis can be difficult to establish in milder cases, especially if VLCFA concentration in plasma is not or only mildly elevated. We report on siblings in which initial measurement of plasma VLCFA did not indicate a peroxisomal disease. Nevertheless, cMRI showed a pattern typical for an inborn peroxisomal disease with cerebral and cerebellar leukencephalopathy, perisylvic polymicrogyria, and frontoparietal pachygyria. Repeated measurements of peroxisomal metabolites in plasma prompted by the cMRI findings showed values in the upper normal or mildly elevated range and led to further diagnostic steps. The diagnosis of a type III DBPD with a missense mutation (T15A) in the HSD17B4 gene, coding for D-bifunctional protein (DBP), could be established. We conclude that a typical \"peroxisomal pattern'' in cMRI including cerebral and cerebellar leukencephalopathy, perisylvic polymicrogyria and pachygyria is a valuable clue to the diagnosis of DBPD, especially in cases with no or only very mild abnormalities in plasma. (C) 2010 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/ajmg.a.33677"],["dc.identifier.gro","3142834"],["dc.identifier.isi","000284005700028"],["dc.identifier.pmid","20949532"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/282"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-liss"],["dc.relation.issn","1552-4825"],["dc.title","Typical cMRI Pattern as Diagnostic Clue for D-Bifunctional Protein Deficiency Without Apparent Biochemical Abnormalities in Plasma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]