Wollnik, Bernd

[["dc.bibliographiccitation.journal","Human Genetics"],["dc.contributor.author","Schmidt, Julia"],["dc.contributor.author","Goergens, Jonas"],["dc.contributor.author","Pochechueva, Tatiana"],["dc.contributor.author","Kotter, Annika"],["dc.contributor.author","Schwenzer, Niko"],["dc.contributor.author","Sitte, Maren"],["dc.contributor.author","Werner, Gesa"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2021-10-01T09:58:42Z"],["dc.date.available","2021-10-01T09:58:42Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract The highly conserved YrdC domain-containing protein (YRDC) interacts with the well-described KEOPS complex, regulating specific tRNA modifications to ensure accurate protein synthesis. Previous studies have linked the KEOPS complex to a role in promoting telomere maintenance and controlling genome integrity. Here, we report on a newborn with a severe neonatal progeroid phenotype including generalized loss of subcutaneous fat, microcephaly, growth retardation, wrinkled skin, renal failure, and premature death at the age of 12 days. By trio whole-exome sequencing, we identified a novel homozygous missense mutation, c.662T > C, in YRDC affecting an evolutionary highly conserved amino acid (p.Ile221Thr). Functional characterization of patient-derived dermal fibroblasts revealed that this mutation impairs YRDC function and consequently results in reduced t 6 A modifications of tRNAs. Furthermore, we established and performed a novel and highly sensitive 3-D Q-FISH analysis based on single-telomere detection to investigate the impact of YRDC on telomere maintenance. This analysis revealed significant telomere shortening in YRDC-mutant cells. Moreover, single-cell RNA sequencing analysis of YRDC-mutant fibroblasts revealed significant transcriptome-wide changes in gene expression, specifically enriched for genes associated with processes involved in DNA repair. We next examined the DNA damage response of patient’s dermal fibroblasts and detected an increased susceptibility to genotoxic agents and a global DNA double-strand break repair defect. Thus, our data suggest that YRDC may affect the maintenance of genomic stability. Together, our findings indicate that biallelic variants in YRDC result in a developmental disorder with progeroid features and might be linked to increased genomic instability and telomere shortening."],["dc.identifier.doi","10.1007/s00439-021-02347-3"],["dc.identifier.pii","2347"],["dc.identifier.pmid","34545459"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90122"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/347"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/406"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["dc.relation","SFB 1002 | S02: Hochauflösende Fluoreszenzmikroskopie und integrative Datenanalyse"],["dc.relation.eissn","1432-1203"],["dc.relation.issn","0340-6717"],["dc.relation.workinggroup","RG Lehnart"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights","CC BY 4.0"],["dc.title","Biallelic variants in YRDC cause a developmental disorder with progeroid features"],["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","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","591"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Human Mutation"],["dc.bibliographiccitation.lastpage","599"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Saida, Ken"],["dc.contributor.author","DeMarzo, Danielle"],["dc.contributor.author","Miyake, Noriko"],["dc.contributor.author","Fujita, Atsushi"],["dc.contributor.author","Yang Tan, Tiong"],["dc.contributor.author","White, Susan M."],["dc.contributor.author","Wadley, Alexandrea"],["dc.contributor.author","Toliat, Mohammad R."],["dc.contributor.author","Motameny, Susanne"],["dc.contributor.author","Franitza, Marek"],["dc.contributor.author","Stutterd, Chloe A."],["dc.contributor.author","Chong, Pin F."],["dc.contributor.author","Kira, Ryutaro"],["dc.contributor.author","Sengoku, Toru"],["dc.contributor.author","Ogata, Kazuhiro"],["dc.contributor.author","Guillen Sacoto, Maria J."],["dc.contributor.author","Fresen, Christine"],["dc.contributor.author","Beck, Bodo B."],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Dieterich, Christoph"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Matsumoto, Naomichi"],["dc.contributor.author","Altmüller, Janine"],["dc.date.accessioned","2020-12-10T14:06:39Z"],["dc.date.available","2020-12-10T14:06:39Z"],["dc.date.issued","2019"],["dc.description.abstract","RHOA is a member of the Rho family of GTPases that are involved in fundamental cellular processes including cell adhesion, migration, and proliferation. RHOA can stimulate the formation of stress fibers and focal adhesions and is a key regulator of actomyosin dynamics in various tissues. In a Genematcher-facilitated collaboration, we were able to identify four unrelated individuals with a specific phenotype characterized by hypopigmented areas of the skin, dental anomalies, body asymmetry, and limb length discrepancy due to hemihypotrophy of one half of the body, as well as brain magnetic resonance imaging (MRI) anomalies. Using whole-exome and ultra-deep amplicon sequencing and comparing genomic data of affected and unaffected areas of the skin, we discovered that all four individuals carried the identical RHOA missense variant, c.139G>A; p.Glu47Lys, in a postzygotic state. Molecular modeling and in silico analysis of the affected p.Glu47Lys residue in RHOA indicated that this exchange is predicted to specifically alter the interaction of RHOA with its downstream effectors containing a PKN-type binding domain and thereby disrupts its ability to activate signaling. Our findings indicate that the recurrent postzygotic RHOA missense variant p.Glu47Lys causes a specific mosaic disorder in humans."],["dc.description.sponsorship","AMED http://dx.doi.org/10.13039/100009619"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","JSPS http://dx.doi.org/10.13039/501100001691"],["dc.description.sponsorship","Takeda Science Foundation http://dx.doi.org/10.13039/100007449"],["dc.description.sponsorship","Ministry of Health, Labour and Welfare http://dx.doi.org/10.13039/501100003478"],["dc.identifier.doi","10.1002/humu.23964"],["dc.identifier.eissn","1098-1004"],["dc.identifier.issn","1059-7794"],["dc.identifier.pmid","31821646"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17077"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69974"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/10"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1098-1004"],["dc.relation.issn","1059-7794"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.subject.ddc","610"],["dc.title","The recurrent postzygotic pathogenic variant p.Glu47Lys in RHOA causes a novel recognizable neuroectodermal phenotype"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","622"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","American journal of human genetics"],["dc.bibliographiccitation.lastpage","632"],["dc.bibliographiccitation.volume","95"],["dc.contributor.author","Hussain, Muhammad Sajid"],["dc.contributor.author","Battaglia, Agatino"],["dc.contributor.author","Szczepanski, Sandra"],["dc.contributor.author","Kaygusuz, Emrah"],["dc.contributor.author","Toliat, Mohammad Reza"],["dc.contributor.author","Sakakibara, Shin-ichi"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Gudrun"],["dc.contributor.author","Moosa, Shahida"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Beleggia, Filippo"],["dc.contributor.author","Tinschert, Sigrid"],["dc.contributor.author","Clayton-Smith, Jill"],["dc.contributor.author","Vasudevan, Pradeep"],["dc.contributor.author","Urquhart, Jill E."],["dc.contributor.author","Donnai, Dian"],["dc.contributor.author","Fryer, Alan"],["dc.contributor.author","Percin, E. Ferda"],["dc.contributor.author","Brancati, Francesco"],["dc.contributor.author","Dobbie, Angus"],["dc.contributor.author","Smigiel, Robert"],["dc.contributor.author","Gillessen-Kaesbach, Gabriele"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Noegel, Angelika Anna"],["dc.contributor.author","Newman, William G."],["dc.contributor.author","Nürnberg, Peter"],["dc.date.accessioned","2017-09-07T11:45:24Z"],["dc.date.available","2017-09-07T11:45:24Z"],["dc.date.issued","2014"],["dc.description.abstract","Filippi syndrome is a rare, presumably autosomal-recessive disorder characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features, including a broad nasal bridge and underdeveloped alae nasi. Some affected individuals have intellectual disability, seizures, undescended testicles in males, and teeth and hair abnormalities. We performed homozygosity mapping and whole-exome sequencing in a Sardinian family with two affected children and identified a homozygous frameshift mutation, c.571dupA (p.Ile191Asnfs 6), in CKAP2L, encoding the protein cytoskeleton-associated protein 2-like (CKAP2L). The function of this protein was unknown until it was rediscovered in mice as Radmis (radial fiber and mitotic spindle) and shown to play a pivotal role in cell division of neural progenitors. Sanger sequencing of CKAP2L in a further eight unrelated individuals with clinical features consistent with Filippi syndrome revealed biallelic mutations in four subjects. In contrast to wild-type lymphoblastoid cell lines (LCLs), dividing LCLs established from the individuals homozygous for the c.571dupA mutation did not show CKAP2L at the spindle poles. Furthermore, in cells from the affected individuals, we observed an increase in the number of disorganized spindle microtubules owing to multipolar configurations and defects in chromosome segregation. The observed cellular phenotypes are in keeping with data from in vitro and in vivo knockdown studies performed in human cells and mice, respectively. Our findings show that loss-of-function mutations in CKAP2L are a major cause of Filippi syndrome."],["dc.identifier.doi","10.1016/j.ajhg.2014.10.008"],["dc.identifier.gro","3142020"],["dc.identifier.isi","000344845000013"],["dc.identifier.pmid","25439729"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3656"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Koln Fortune; Center for Molecular Medicine Cologne"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.eissn","1537-6605"],["dc.relation.issn","0002-9297"],["dc.title","Mutations in CKAP2L, the Human Homo log of the Mouse Radmis Gene, Cause Filippi Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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","728"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics"],["dc.bibliographiccitation.lastpage","733"],["dc.bibliographiccitation.volume","170"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Wieczorek, Dagmar"],["dc.contributor.author","Boegershausen, Nina"],["dc.contributor.author","Beleggia, Filippo"],["dc.contributor.author","Moeller-Hartmann, Claudia"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:54:36Z"],["dc.date.available","2017-09-07T11:54:36Z"],["dc.date.issued","2016"],["dc.description.abstract","Using whole-exome sequencing, we identified a homozygous acceptor splice-site mutation in intron 6 of the KATNB1 gene in a patient from a consanguineous Turkish family who presented with congenital microcephaly, lissencephaly, short stature, polysyndactyly, and dental abnormalities. cDNA analysis revealed complete loss of the natural acceptor splice-site resulting either in the usage of an alternative, exonic acceptor splice-site inducing a frame-shift and premature protein truncation or, to a minor extent, in complete skipping of exon 7. Both effects most likely lead to complete loss of KATNB1 function. Homozygous and compound heterozygous mutations in KATNB1 have very recently been described as a cause of microcephaly with brain malformations and seizures. We extend the KATNB1 associated phenotype by describing a syndrome characterized by primordial dwarfism, lissencephaly, polysyndactyly, and dental anomalies, which is caused by a homozygous truncating KATNB1 mutation. (c) 2015 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/ajmg.a.37484"],["dc.identifier.gro","3141719"],["dc.identifier.isi","000373098900028"],["dc.identifier.pmid","26640080"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/313"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.eissn","1552-4833"],["dc.relation.issn","1552-4825"],["dc.title","A Syndrome of Microcephaly, Short Stature, Polysyndactyly, and Dental Anomalies Caused by a Homozygous KATNB1 Mutation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1363"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Human Genetics"],["dc.bibliographiccitation.lastpage","1379"],["dc.bibliographiccitation.volume","139"],["dc.contributor.author","Ufartes, Roser"],["dc.contributor.author","Berger, Hanna"],["dc.contributor.author","Till, Katharina"],["dc.contributor.author","Salinas, Gabriela"],["dc.contributor.author","Sturm, Marc"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Funke, Rudolf"],["dc.contributor.author","Apeshiotis, Neophytos"],["dc.contributor.author","Langen, Hendrik"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Borchers, Annette"],["dc.contributor.author","Pauli, Silke"],["dc.date.accessioned","2020-12-10T14:10:38Z"],["dc.date.available","2020-12-10T14:10:38Z"],["dc.date.issued","2020"],["dc.description.abstract","We report truncating de novo variants in specific exons of FBRSL1 in three unrelated children with an overlapping syndromic phenotype with respiratory insufficiency, postnatal growth restriction, microcephaly, global developmental delay and other malformations. The function of FBRSL1 is largely unknown. Interestingly, mutations in the FBRSL1 paralogue AUTS2 lead to an intellectual disability syndrome (AUTS2 syndrome). We determined human FBRSL1 transcripts and describe protein-coding forms by Western blot analysis as well as the cellular localization by immunocytochemistry stainings. All detected mutations affect the two short N-terminal isoforms, which show a ubiquitous expression in fetal tissues. Next, we performed a Fbrsl1 knockdown in Xenopus laevis embryos to explore the role of Fbrsl1 during development and detected craniofacial abnormalities and a disturbance in neurite outgrowth. The aberrant phenotype in Xenopus laevis embryos could be rescued with a human N-terminal isoform, while the long isoform and the N-terminal isoform containing the mutation p.Gln163* isolated from a patient could not rescue the craniofacial defects caused by Fbrsl1 depletion. Based on these data, we propose that the disruption of the validated N-terminal isoforms of FBRSL1 at critical timepoints during embryogenesis leads to a hitherto undescribed complex neurodevelopmental syndrome."],["dc.identifier.doi","10.1007/s00439-020-02175-x"],["dc.identifier.pmid","32424618"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70825"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/184"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights","CC BY 4.0"],["dc.title","De novo mutations in FBRSL1 cause a novel recognizable malformation and intellectual disability syndrome"],["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","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.issue","9"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part A"],["dc.bibliographiccitation.volume","170"],["dc.contributor.author","Moosa, Shahida"],["dc.contributor.author","Fano, Virginia"],["dc.contributor.author","Obregon, Maria Gabriela"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Nishimura, Gen"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:54:27Z"],["dc.date.available","2017-09-07T11:54:27Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1002/ajmg.a.37884"],["dc.identifier.gro","3145170"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2876"],["dc.notes.intern","Crossref Import"],["dc.notes.status","public"],["dc.publisher","Wiley-Blackwell"],["dc.relation.issn","1552-4825"],["dc.title","Cover Image, Volume 170A, Number 9, September 2016"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]