Wollnik, Bernd

[["dc.bibliographiccitation.firstpage","975"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","991"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Borchert, Thomas"],["dc.contributor.author","Hübscher, Daniela"],["dc.contributor.author","Guessoum, Celina I."],["dc.contributor.author","Lam, Tuan-Dinh D."],["dc.contributor.author","Ghadri, Jelena R."],["dc.contributor.author","Schellinger, Isabel N."],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Liaw, Norman Y."],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Haas, Jan"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Huber, Mia A."],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Raaz, Uwe"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Lüscher, Thomas F."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Templin, Christian"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.date.accessioned","2018-04-23T11:48:11Z"],["dc.date.available","2018-04-23T11:48:11Z"],["dc.date.issued","2017"],["dc.description.abstract","Background Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. Objectives The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS. Methods Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function. Results Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate–dependent protein kinase A–mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β1-adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function. Conclusions Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype."],["dc.identifier.doi","10.1016/j.jacc.2017.06.061"],["dc.identifier.gro","3142333"],["dc.identifier.pmid","28818208"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16489"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13468"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/204"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation.issn","0735-1097"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.relation.workinggroup","RG Dressel"],["dc.relation.workinggroup","RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Wollnik"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","416"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurology"],["dc.bibliographiccitation.lastpage","419"],["dc.bibliographiccitation.volume","256"],["dc.contributor.author","Durmaz, Burak"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Cogulu, Ozgur"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Tekgul, Hasan"],["dc.contributor.author","Hazan, Filiz"],["dc.contributor.author","Ozkinay, Ferda"],["dc.date.accessioned","2017-09-07T11:47:34Z"],["dc.date.available","2017-09-07T11:47:34Z"],["dc.date.issued","2009"],["dc.description.abstract","Pontocerebellar hypoplasia (PCH) is a heterogeneous group of disorders characterized by abnormally small cerebellum and brainstem. Recently a rare, novel form of PCH has been reported called cerebellar atrophy with progressive microcephaly (CLAM). Here we report a second family of CLAM with additional phenotypic features and novel molecular findings. Three-year old index patient had severe developmental delay and presented with short stature and microcephaly. Her cranial magnetic resonance imaging revealed hypoplasia of the cerebellum, brainstem and cerebrum associated with hypoplasia of the corpus callosum. Brainstem auditory evoked potentials revealed hearing loss and visual evoked potentials confirmed the optic atrophy. She also had seizures with two posterior epileptic foci on electroencephalogram. Molecular analysis revealed a homozygous haplotype between the markers D7S802 and D7S630 within the originally linked region, narrowing the critical region from 20 Mb to 7 Mb. Two highly relevant candidate genes, CROT and SLC25A40 located in this region were sequenced, but no causative mutations identified. Our case provides additional clinical characteristics on the previously described features of this new entity, and reducing the critical region will now allow systematic positional cloning efforts to identify the causative gene."],["dc.identifier.doi","10.1007/s00415-009-0094-0"],["dc.identifier.gro","3143145"],["dc.identifier.isi","000265732800015"],["dc.identifier.pmid","19277761"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/627"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Dr Dietrich Steinkopff Verlag"],["dc.relation.issn","0340-5354"],["dc.title","Pontocerebellar hypoplasia type III (CLAM): Extended phenotype and novel molecular findings"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","836"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","843"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Moosa, Shahida"],["dc.contributor.author","Yamamoto, Guilherme L."],["dc.contributor.author","Garbes, Lutz"],["dc.contributor.author","Keupp, Katharina"],["dc.contributor.author","Beleza-Meireles, Ana"],["dc.contributor.author","Moreno, Carolina Araujo"],["dc.contributor.author","Valadares, Eugenia Ribeiro"],["dc.contributor.author","de Sousa, Sérgio B."],["dc.contributor.author","Maia, Sofia"],["dc.contributor.author","Saraiva, Jorge"],["dc.contributor.author","Honjo, Rachel S."],["dc.contributor.author","Kim, Chong Ae"],["dc.contributor.author","Cabral de Menezes, Hamilton"],["dc.contributor.author","Lausch, Ekkehart"],["dc.contributor.author","Lorini, Pablo Villavicencio"],["dc.contributor.author","Lamounier, Arsonval"],["dc.contributor.author","Carniero, Tulio Canella Bezerra"],["dc.contributor.author","Giunta, Cecilia"],["dc.contributor.author","Rohrbach, Marianne"],["dc.contributor.author","Janner, Marco"],["dc.contributor.author","Semler, Oliver"],["dc.contributor.author","Beleggia, Filippo"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Reintjes, Nadine"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Cavalcanti, Denise P."],["dc.contributor.author","Zabel, Bernhard"],["dc.contributor.author","Warman, Matthew L."],["dc.contributor.author","Bertola, Debora R."],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Netzer, Christian"],["dc.date.accessioned","2020-12-10T14:22:21Z"],["dc.date.available","2020-12-10T14:22:21Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.ajhg.2019.08.008"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71587"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/19"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG Wollnik"],["dc.title","Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1454"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Human Mutation"],["dc.bibliographiccitation.lastpage","1471"],["dc.bibliographiccitation.volume","43"],["dc.contributor.affiliation","Bögershausen, Nina; 1\r\nInstitute of Human Genetics\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Krawczyk, Hannah E.; 1\r\nInstitute of Human Genetics\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Jamra, Rami A.; 2\r\nInstitute of Human Genetics\r\nUniversity of Leipzig Medical Center\r\nLeipzig Germany"],["dc.contributor.affiliation","Lin, Sheng‐Jia; 3\r\nGenes & Human Disease Research Program\r\nOklahoma Medical Research Foundation\r\nOklahoma City Oklahoma USA"],["dc.contributor.affiliation","Yigit, Gökhan; 1\r\nInstitute of Human Genetics\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Hüning, Irina; 4\r\nInstitut für Humangenetik\r\nUniversitätsklinikum Schleswig‐Holstein\r\nLübeck Germany"],["dc.contributor.affiliation","Polo, Anna M.; 5\r\nMVZ Labor Krone\r\nFilialpraxis für Humangenetik\r\nBielefeld Germany"],["dc.contributor.affiliation","Vona, Barbara; 1\r\nInstitute of Human Genetics\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Huang, Kevin; 3\r\nGenes & Human Disease Research Program\r\nOklahoma Medical Research Foundation\r\nOklahoma City Oklahoma USA"],["dc.contributor.affiliation","Schmidt, Julia; 1\r\nInstitute of Human Genetics\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Altmüller, Janine; 7\r\nCologne Center for Genomics (CCG), Faculty of Medicine and University Hospital Cologne\r\nUniversity of Cologne\r\nCologne Germany"],["dc.contributor.affiliation","Luppe, Johannes; 2\r\nInstitute of Human Genetics\r\nUniversity of Leipzig Medical Center\r\nLeipzig Germany"],["dc.contributor.affiliation","Platzer, Konrad; 2\r\nInstitute of Human Genetics\r\nUniversity of Leipzig Medical Center\r\nLeipzig Germany"],["dc.contributor.affiliation","Dörgeloh, Beate B.; 10\r\nDepartment of Pediatric Hematology and Oncology\r\nHannover Medical School\r\nHannover Germany"],["dc.contributor.affiliation","Busche, Andreas; 11\r\nInstitut für Humangenetik\r\nWestfälische Wilhelms‐Universität Münster\r\nMünster Germany"],["dc.contributor.affiliation","Biskup, Saskia; 12\r\nCeGaT GmbH\r\nCenter for Genomics and Transcriptomics\r\nTübingen Germany"],["dc.contributor.affiliation","Mendes, Marisa I.; 13\r\nLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology and Metabolism, Amsterdam Neuroscience\r\nAmsterdam UMC\r\nAmsterdam Netherlands"],["dc.contributor.affiliation","Smith, Desiree E. C.; 13\r\nLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology and Metabolism, Amsterdam Neuroscience\r\nAmsterdam UMC\r\nAmsterdam Netherlands"],["dc.contributor.affiliation","Salomons, Gajja S.; 13\r\nLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology and Metabolism, Amsterdam Neuroscience\r\nAmsterdam UMC\r\nAmsterdam Netherlands"],["dc.contributor.affiliation","Zibat, Arne; 1\r\nInstitute of Human Genetics\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Bültmann, Eva; 14\r\nInstitute of Diagnostic and Interventional Neuroradiology\r\nHannover Medical School\r\nHannover Germany"],["dc.contributor.affiliation","Nürnberg, Peter; 7\r\nCologne Center for Genomics (CCG), Faculty of Medicine and University Hospital Cologne\r\nUniversity of Cologne\r\nCologne Germany"],["dc.contributor.affiliation","Spielmann, Malte; 4\r\nInstitut für Humangenetik\r\nUniversitätsklinikum Schleswig‐Holstein\r\nLübeck Germany"],["dc.contributor.affiliation","Lemke, Johannes R.; 2\r\nInstitute of Human Genetics\r\nUniversity of Leipzig Medical Center\r\nLeipzig Germany"],["dc.contributor.affiliation","Li, Yun; 1\r\nInstitute of Human Genetics\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Zenker, Martin; 16\r\nInstitute of Human Genetics\r\nOtto‐von‐Guericke University Magdeburg\r\nMagdeburg Germany"],["dc.contributor.affiliation","Varshney, Gaurav K.; 3\r\nGenes & Human Disease Research Program\r\nOklahoma Medical Research Foundation\r\nOklahoma City Oklahoma USA"],["dc.contributor.affiliation","Hillen, Hauke S.; 17\r\nResearch Group Structure and Function of Molecular Machines\r\nMax Planck Institute for Multidisciplinary Sciences\r\nGöttingen Germany"],["dc.contributor.affiliation","Kratz, Christian P.; 10\r\nDepartment of Pediatric Hematology and Oncology\r\nHannover Medical School\r\nHannover Germany"],["dc.contributor.author","Bögershausen, Nina"],["dc.contributor.author","Krawczyk, Hannah E."],["dc.contributor.author","Jamra, Rami A."],["dc.contributor.author","Lin, Sheng‐Jia"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Hüning, Irina"],["dc.contributor.author","Polo, Anna M."],["dc.contributor.author","Vona, Barbara"],["dc.contributor.author","Huang, Kevin"],["dc.contributor.author","Schmidt, Julia"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Luppe, Johannes"],["dc.contributor.author","Platzer, Konrad"],["dc.contributor.author","Dörgeloh, Beate B."],["dc.contributor.author","Busche, Andreas"],["dc.contributor.author","Biskup, Saskia"],["dc.contributor.author","Mendes, Marisa I."],["dc.contributor.author","Smith, Desiree E. C."],["dc.contributor.author","Salomons, Gajja S."],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Bültmann, Eva"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Spielmann, Malte"],["dc.contributor.author","Lemke, Johannes R."],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Zenker, Martin"],["dc.contributor.author","Varshney, Gaurav K."],["dc.contributor.author","Hillen, Hauke S."],["dc.contributor.author","Kratz, Christian P."],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2022-11-28T09:45:52Z"],["dc.date.available","2022-11-28T09:45:52Z"],["dc.date.issued","2022-07-21"],["dc.date.updated","2022-11-27T10:11:29Z"],["dc.description.abstract","Based on the identification of novel variants in aminoacyl‐tRNA synthetase (ARS) genes WARS1 and SARS1, the authors define an emerging disease spectrum related to all type 1 ARS genes: aminoacyl‐tRNA synthetase‐related developmental disorders with or without microcephaly (ARS‐DDM).\r\n\r\nimage"],["dc.description.abstract","Aminoacylation of transfer RNA (tRNA) is a key step in protein biosynthesis, carried out by highly specific aminoacyl-tRNA synthetases (ARSs). ARSs have been implicated in autosomal dominant and autosomal recessive human disorders. Autosomal dominant variants in tryptophanyl-tRNA synthetase 1 (WARS1) are known to cause distal hereditary motor neuropathy and Charcot-Marie-Tooth disease, but a recessively inherited phenotype is yet to be clearly defined. Seryl-tRNA synthetase 1 (SARS1) has rarely been implicated in an autosomal recessive developmental disorder. Here, we report five individuals with biallelic missense variants in WARS1 or SARS1, who presented with an overlapping phenotype of microcephaly, developmental delay, intellectual disability, and brain anomalies. Structural mapping showed that the SARS1 variant is located directly within the enzyme's active site, most likely diminishing activity, while the WARS1 variant is located in the N-terminal domain. We further characterize the identified WARS1 variant by showing that it negatively impacts protein abundance and is unable to rescue the phenotype of a CRISPR/Cas9 wars1 knockout zebrafish model. In summary, we describe two overlapping autosomal recessive syndromes caused by variants in WARS1 and SARS1, present functional insights into the pathogenesis of the WARS1-related syndrome and define an emerging disease spectrum: ARS-related developmental disorders with or without microcephaly."],["dc.description.sponsorship","Deutsches Zentrum für Herz‐Kreislaufforschung http://dx.doi.org/10.13039/100010447"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","Presbyterian Health Foundation http://dx.doi.org/10.13039/100001298"],["dc.description.sponsorship","University Medical Center Göttingen"],["dc.description.sponsorship","Oklahoma Medical Research Foundation http://dx.doi.org/10.13039/100008907"],["dc.identifier.doi","10.1002/humu.24430"],["dc.identifier.pmid","35790048"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117321"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/517"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/180"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/34"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | St01: Structure and distribution of ribosomes at the inner mitochondrial membrane"],["dc.relation.eissn","1098-1004"],["dc.relation.issn","1059-7794"],["dc.relation.workinggroup","RG Wollnik"],["dc.relation.workinggroup","RG Hillen (Structure and Function of Molecular Machines)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","WARS1 and SARS1: Two tRNA synthetases implicated in autosomal recessive microcephaly"],["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","919"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","American journal of human genetics"],["dc.bibliographiccitation.lastpage","927"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","von Ameln, Simon"],["dc.contributor.author","Wang, Geng"],["dc.contributor.author","Boulouiz, Redouane"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Smith, Geoffrey M."],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Pogoda, Hans-Martin"],["dc.contributor.author","Nürnberg, Gudrun"],["dc.contributor.author","Stiller, Barbara"],["dc.contributor.author","Volk, Alexander E."],["dc.contributor.author","Borck, Guntram"],["dc.contributor.author","Hong, Jason S."],["dc.contributor.author","Goodyear, Richard J."],["dc.contributor.author","Abidi, Omar"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Hofmann, Kay"],["dc.contributor.author","Richardson, Gu Y. P."],["dc.contributor.author","Hammerschmidt, Matthias"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Koehler, Carla M."],["dc.contributor.author","Teitell, Michael A."],["dc.contributor.author","Barakat, Abdelhamid"],["dc.contributor.author","Kubisch, Christian"],["dc.date.accessioned","2017-09-07T11:48:21Z"],["dc.date.available","2017-09-07T11:48:21Z"],["dc.date.issued","2012"],["dc.description.abstract","A subset of nuclear-encoded RNAs has to be imported into mitochondria for the proper replication and transcription of the mitochondrial genome and, hence, for proper mitochondrial function. Polynucleotide phosphorylase (PNPase or PNPT1) is one of the very few components known to be involved in this poorly characterized process in mammals. At the organismal level, however, the effect of PNPase dysfunction and impaired mitochondrial RNA import are unknown. By positional cloning, we identified a homozygous PNPT1 missense mutation (c.1424A>G predicting the protein substitution p.Glu475Gly) of a highly conserved PNPase residue within the second RNase-PH domain in a family affected by autosomal-recessive nonsyndromic hearing impairment. In vitro analyses in bacteria, yeast, and mammalian cells showed that the identified mutation results in a hypofunctional protein leading to disturbed PNPase trimerization and impaired mitochondrial RNA import. Immunohistochemistry revealed strong PNPase staining in the murine cochlea, including the sensory hair cells and the auditory ganglion neurons. In summary, we show that a component of the mitochondrial RNA-import machinery is specifically required for auditory function."],["dc.identifier.doi","10.1016/j.ajhg.2012.09.002"],["dc.identifier.gro","3142441"],["dc.identifier.isi","000311011400015"],["dc.identifier.pmid","23084290"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8318"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","0002-9297"],["dc.title","A Mutation in PNPT1, Encoding Mitochondrial-RNA-Import Protein PNPase, Causes Hereditary Hearing Loss"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","580"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Molecular Genetics & Genomic Medicine"],["dc.bibliographiccitation.lastpage","584"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Moosa, Shahida"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Lyngbye, Troels"],["dc.contributor.author","Christensen, Rikke"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Vogel, Ida"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2018-04-23T11:49:11Z"],["dc.date.available","2018-04-23T11:49:11Z"],["dc.date.issued","2017"],["dc.description.abstract","Background Very recently, compound heterozygous loss‐of‐function mutations in TELO2 were shown to underlie the newly‐described You‐Hoover‐Fong syndrome. TELO2 forms part of the co‐chaperone triple T complex (TTT complex), which plays an important role in the maturation and stabilization of the phosphatidylinositol 3‐kinase‐related protein kinases (PIKKs). Patients with mutations in TELO2 present with microcephaly and associated intellectual disability, postnatal growth retardation and dysmorphic features. Here, we describe Danish sisters with two novel mutations in TELO2. In particular, we highlight the clinical features of the 22‐year index patient, which are more severe than the original patients described, thereby expanding the clinical spectrum of YHFS. Methods The index patient was clinically examined and subsequently exome sequencing on her DNA was performed using the NimbleGen SeqCap EZ Human Exome Library v2.0 enrichment kit on an Illumina HiSeq2000 sequencer. Results Two novel, compound heterozygous mutations in TELO2 were identified in the index patient and her deceased older sister. Both have clinical features in keeping with the original YHFS patients, although the index patient seems to represent the severe end of the clinical spectrum with very marked prenatal onset growth retardation and microcephaly, severe global developmental delay and facial dysmorphic features. Additional clinical findings include eye anomalies (bilateral congenital cataracts, retinitis pigmentosa, convergent squint), bilateral conductive hearing loss, an abnormal kidney and seizures. Conclusion This report of Danish siblings with YHFS serves to expand the presentation of this new syndrome to include features in keeping with a form of microcephalic primordial dwarfism on the severe end of the clinical spectrum, and adds two novel mutations to the TELO2 mutational spectrum."],["dc.identifier.doi","10.1002/mgg3.287"],["dc.identifier.gro","3142502"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13656"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","2324-9269"],["dc.title","Novel compound heterozygous mutations in TELO2 in a patient with severe expression of You-Hoover-Fong syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","837"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of Medical Genetics"],["dc.bibliographiccitation.lastpage","846"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Paolacci, Stefano"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Agolini, Emanuele"],["dc.contributor.author","Bellacchio, Emanuele"],["dc.contributor.author","Arboleda-Bustos, Carlos E"],["dc.contributor.author","Carrero, Dido"],["dc.contributor.author","Bertola, Debora"],["dc.contributor.author","Al-Gazali, Lihadh"],["dc.contributor.author","Alders, Mariel"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Arboleda, Gonzalo"],["dc.contributor.author","Beleggia, Filippo"],["dc.contributor.author","Bruselles, Alessandro"],["dc.contributor.author","Ciolfi, Andrea"],["dc.contributor.author","Gillessen-Kaesbach, Gabriele"],["dc.contributor.author","Krieg, Thomas"],["dc.contributor.author","Mohammed, Shehla"],["dc.contributor.author","Müller, Christian"],["dc.contributor.author","Novelli, Antonio"],["dc.contributor.author","Ortega, Jenny"],["dc.contributor.author","Sandoval, Adrian"],["dc.contributor.author","Velasco, Gloria"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Arboleda, Humberto"],["dc.contributor.author","Lopez-Otin, Carlos"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Tartaglia, Marco"],["dc.contributor.author","Hennekam, Raoul C"],["dc.date.accessioned","2020-12-10T18:37:16Z"],["dc.date.available","2020-12-10T18:37:16Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1136/jmedgenet-2018-105528"],["dc.identifier.pmid","30323018"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/76895"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/238"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation.workinggroup","RG Wollnik"],["dc.title","Specific combinations of biallelic POLR3A variants cause Wiedemann-Rautenstrauch syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","341"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Genetics in Medicine"],["dc.bibliographiccitation.lastpage","351"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Schröder, Simone"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Bader, Ingrid"],["dc.contributor.author","Bevot, Andrea"],["dc.contributor.author","Biskup, Saskia"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Christoph Korenke, G."],["dc.contributor.author","Kottke, Raimund"],["dc.contributor.author","Mayr, Johannes A."],["dc.contributor.author","Preisel, Martin"],["dc.contributor.author","Toelle, Sandra P."],["dc.contributor.author","Wente-Schulz, Sarah"],["dc.contributor.author","Wortmann, Saskia B."],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Boltshauser, Eugen"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Brockmann, Knut"],["dc.date.accessioned","2021-04-14T08:31:50Z"],["dc.date.available","2021-04-14T08:31:50Z"],["dc.date.issued","2020"],["dc.description.abstract","Purpose\r\n\r\nThis study aimed to delineate the genetic basis of congenital ocular motor apraxia (COMA) in patients not otherwise classifiable.\r\nMethods\r\n\r\nWe compiled clinical and neuroimaging data of individuals from six unrelated families with distinct clinical features of COMA who do not share common diagnostic characteristics of Joubert syndrome or other known genetic conditions associated with COMA. We used exome sequencing to identify pathogenic variants and functional studies in patient-derived fibroblasts.\r\nResults\r\n\r\nIn 15 individuals, we detected familial as well as de novo heterozygous truncating causative variants in the Suppressor of Fused (SUFU) gene, a negative regulator of the Hedgehog (HH) signaling pathway. Functional studies showed no differences in cilia occurrence, morphology, or localization of ciliary proteins, such as smoothened. However, analysis of expression of HH signaling target genes detected a significant increase in the general signaling activity in COMA patient–derived fibroblasts compared with control cells. We observed higher basal HH signaling activity resulting in increased basal expression levels of GLI1, GLI2, GLI3, and Patched1. Neuroimaging revealed subtle cerebellar changes, but no full-blown molar tooth sign.\r\nConclusion\r\n\r\nTaken together, our data imply that the clinical phenotype associated with heterozygous truncating germline variants in SUFU is a forme fruste of Joubert syndrome."],["dc.identifier.doi","10.1038/s41436-020-00979-w"],["dc.identifier.pmid","33024317"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83726"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/80"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1530-0366"],["dc.relation.issn","1098-3600"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights","CC BY 4.0"],["dc.title","Heterozygous truncating variants in SUFU cause congenital ocular motor apraxia"],["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","352"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Molecular Genetics and Metabolism"],["dc.bibliographiccitation.lastpage","361"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Dimopoulou, Aikaterini"],["dc.contributor.author","Fischer, Björn"],["dc.contributor.author","Gardeitchik, Thatjana"],["dc.contributor.author","Schroeter, Phillipe"],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Schlack, Claire"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Brum, Jaime Moritz"],["dc.contributor.author","Barisic, Ingeborg"],["dc.contributor.author","Castori, Marco"],["dc.contributor.author","Spaich, Christiane"],["dc.contributor.author","Fletcher, Elaine"],["dc.contributor.author","Mahayri, Zeina"],["dc.contributor.author","Bhat, Meenakshi"],["dc.contributor.author","Girisha, Katta M."],["dc.contributor.author","Lachlan, Katherine"],["dc.contributor.author","Johnson, Diana"],["dc.contributor.author","Phadke, Shubha"],["dc.contributor.author","Gupta, Neerja"],["dc.contributor.author","Simandlova, Martina"],["dc.contributor.author","Kabra, Madhulika"],["dc.contributor.author","David, Albert"],["dc.contributor.author","Nijtmans, Leo"],["dc.contributor.author","Chitayat, David"],["dc.contributor.author","Tuysuz, Beyhan"],["dc.contributor.author","Brancati, Francesco"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Van Maldergem, Lionel"],["dc.contributor.author","Morava, Eva"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Kornak, Uwe"],["dc.date.accessioned","2017-09-07T11:47:04Z"],["dc.date.available","2017-09-07T11:47:04Z"],["dc.date.issued","2013"],["dc.description.abstract","Autosomal recessive cutis laxa type 2B (ARCL2B; OMIM # 612940) is a segmental progeroid disorder caused by mutations in PYCR1 encoding pyrroline-5-carboxylate reductase 1, which is part of the conserved proline de novo synthesis pathway. Here we describe 33 patients with PYCR1-related ARCL from 27 families with initial diagnoses varying between wrinkly skin syndrome, gerodermia osteodysplastica, De Barsy syndrome or more severe progeria syndromes. Given the difficult differential diagnosis of ARCL syndromes we performed a systematic comparison of clinical features of PYCR1-related ARCL. Intrauterine growth retardation, a characteristic triangular facial gestalt, psychomotor retardation, and hypotonia were the most relevant distinctive hallmarks of ARCL due to proline de novo synthesis defects. Corneal clouding or cataracts, athetoid movements, and finger contractures were rather rare features, but had a high predictive value. In our cohort we identified 20 different PYCR1 mutations of which seven were novel. Most of the mutations accumulated in exons 4 to 6. Missense alterations of highly conserved residues were most frequent followed by splice site changes and a single nonsense mutation. Analysis of genotype phenotype correlation revealed that patients with mutations in the first two exons had lower average clinical scores and absent or only mild intellectual disability. Structural analyses predicted interference with PYCR1 multimerization for a subset of missense mutations. These findings have implications for the clinics as well as the pathomechanism of PYCR1-related ARCL. (C) 2013 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.ymgme.2013.08.009"],["dc.identifier.gro","3142262"],["dc.identifier.isi","000326058000025"],["dc.identifier.pmid","24035636"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6331"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.eissn","1096-7206"],["dc.relation.issn","1096-7192"],["dc.title","Genotype phenotype spectrum of PYCR1-related autosomal recessive cutis laxa"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","467"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Molecular Genetics & Genomic Medicine"],["dc.bibliographiccitation.lastpage","480"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Brown, Karen E."],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Pohl, Esther"],["dc.contributor.author","Caliebe, Almuth"],["dc.contributor.author","Zahnleiter, Diana"],["dc.contributor.author","Rosser, Elisabeth"],["dc.contributor.author","Bögershausen, Nina"],["dc.contributor.author","Uyguner, Oya"],["dc.contributor.author","Altunoglu, Umut"],["dc.contributor.author","Nürnberg, Gudrun"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Rauch, Anita"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Thiel, Christian Thomas"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:54:27Z"],["dc.date.available","2017-09-07T11:54:27Z"],["dc.date.issued","2015"],["dc.description.abstract","Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by prenatal proportionate short stature, severe microcephaly, intellectual disability, and characteristic facial features. Here, we describe the novel homozygous splice‐site mutations c.383+1G>C and c.4005‐9A>G in CDK5RAP2 in two consanguineous families with Seckel syndrome. CDK5RAP2 (CEP215) encodes a centrosomal protein which is known to be essential for centrosomal cohesion and proper spindle formation and has been shown to be causally involved in autosomal recessive primary microcephaly. We establish CDK5RAP2 as a disease‐causing gene for Seckel syndrome and show that loss of functional CDK5RAP2 leads to severe defects in mitosis and spindle organization, resulting in cells with abnormal nuclei and centrosomal pattern, which underlines the important role of centrosomal and mitotic proteins in the pathogenesis of the disease. Additionally, we present an intriguing case of possible digenic inheritance in Seckel syndrome: A severely affected child of nonconsanguineous German parents was found to carry heterozygous mutations in CDK5RAP2 and CEP152. This finding points toward a potential additive genetic effect of mutations in CDK5RAP2 and CEP152."],["dc.identifier.doi","10.1002/mgg3.158"],["dc.identifier.gro","3145172"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2878"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","2324-9269"],["dc.title","Mutations in CDK5RAP2 cause Seckel syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]