Krätzner, Ralph

[["dc.bibliographiccitation.firstpage","354"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","363"],["dc.bibliographiccitation.volume","85"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Kraetzner, Ralph"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Helms, Gunther"],["dc.contributor.author","Dechent, Peter"],["dc.contributor.author","Wevers, Ron"],["dc.contributor.author","Grosso, Salvatore"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2019-07-09T11:52:56Z"],["dc.date.available","2019-07-09T11:52:56Z"],["dc.date.issued","2009"],["dc.description.abstract","Sufficient folate supplementation is essential for a multitude of biological processes and diverse organ systems. At least five distinct inherited disorders of folate transport and metabolism are presently known, all of which cause systemic folate deficiency.We identified an inherited brain-specific folate transport defect that is caused by mutations in the folate receptor 1 (FOLR1) gene coding for folate receptor alpha (FRa). Three patients carrying FOLR1 mutations developed progressive movement disturbance, psychomotor decline, and epilepsy and showed severely reduced folate concentrations in the cerebrospinal fluid (CSF). Brain magnetic resonance imaging (MRI) demonstrated profound hypomyelination, and MR-based in vivo metabolite analysis indicated a combined depletion of white-matter choline and inositol. Retroviral transfection of patient cells with either FRa or FRb could rescue folate binding. Furthermore, CSF folate concentrations, as well as glial choline and inositol depletion, were restored by folinic acid therapy and preceded clinical improvements. Our studies not only characterize a previously unknown and treatable disorder of early childhood, but also provide new insights into the folate metabolic pathways involved in postnatal myelination and brain development."],["dc.identifier.doi","10.1016/j.ajhg.2009.08.005."],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6177"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60304"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Folate Receptor Alpha Defect Causes Cerebral Folate Transport Deficiency: A Treatable Neurodegenerative Disorder Associated with Disturbed Myelin Metabolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8733"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","8742"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Thorn, Andrea"],["dc.contributor.author","Steinfeld, Robert"],["dc.contributor.author","Ziegenbein, Marc"],["dc.contributor.author","Grapp, Marcel"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Sheldrick, George M."],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Kraetzner, Ralph"],["dc.date.accessioned","2017-09-07T11:48:25Z"],["dc.date.available","2017-09-07T11:48:25Z"],["dc.date.issued","2012"],["dc.description.abstract","Mutations in the gene of human RNase T2 are associated with white matter disease of the human brain. Although brain abnormalities (bilateral temporal lobe cysts and multifocal white matter lesions) and clinical symptoms (psychomotor impairments, spasticity and epilepsy) are well characterized, the pathomechanism of RNase T2 deficiency remains unclear. RNase T2 is the only member of the Rh/T2/S family of acidic hydrolases in humans. In recent years, new functions such as tumor suppressing properties of RNase T2 have been reported that are independent of its catalytic activity. We determined the X-ray structure of human RNase T2 at 1.6 A resolution. The alpha+beta core fold shows high similarity to those of known T2 RNase structures from plants, while, in contrast, the external loop regions show distinct structural differences. The catalytic features of RNase T2 in presence of bivalent cations were analyzed and the structural consequences of known clinical mutations were investigated. Our data provide further insight into the function of human RNase T2 and may prove useful in understanding its mode of action independent of its enzymatic activity."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2012"],["dc.identifier.doi","10.1093/nar/gks614"],["dc.identifier.gro","3142467"],["dc.identifier.isi","000309464300054"],["dc.identifier.pmid","22735700"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7944"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8607"],["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","Oxford Univ Press"],["dc.relation.issn","0305-1048"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Structure and activity of the only human RNase T2"],["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"]]