Schmidt, Julia

[["dc.bibliographiccitation.artnumber","4091"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Shomroni, Orr"],["dc.contributor.author","Sitte, Maren"],["dc.contributor.author","Schmidt, Julia"],["dc.contributor.author","Parbin, Sabnam"],["dc.contributor.author","Ludewig, Fabian"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Zelarayan, Laura Cecilia"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Salinas, Gabriella"],["dc.date.accessioned","2022-04-01T10:01:43Z"],["dc.date.available","2022-04-01T10:01:43Z"],["dc.date.issued","2022"],["dc.description.abstract","Single cell multi-omics analysis has the potential to yield a comprehensive understanding of the cellular events that underlie the basis of human diseases. The cardinal feature to access this information is the technology used for single-cell isolation, barcoding, and sequencing. Most currently used single-cell RNA-sequencing platforms have limitations in several areas including cell selection, documentation and library chemistry. In this study, we describe a novel high-throughput, full-length, single-cell RNA-sequencing approach that combines the CellenONE isolation and sorting system with the ICELL8 processing instrument. This method offers substantial improvements in single cell selection, documentation and capturing rate. Moreover, it allows the use of flexible chemistry for library preparations and the analysis of living or fixed cells, whole cells independent of sizing and morphology, as well as of nuclei. We applied this method to dermal fibroblasts derived from six patients with different segmental progeria syndromes and defined phenotype associated pathway signatures with variant associated expression modifiers. These results validate the applicability of our method to highlight genotype-expression relationships for molecular phenotyping of individual cells derived from human patients."],["dc.description.sponsorship","Georg-August-Universität Göttingen"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1038/s41598-022-07874-1"],["dc.identifier.pii","7874"],["dc.identifier.pmid","35260714"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105735"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/460"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/424"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation.eissn","2045-2322"],["dc.relation.workinggroup","RG Wollnik"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A novel single-cell RNA-sequencing approach and its applicability connecting genotype to phenotype in ageing disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["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","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.journal","Frontiers in Cell and Developmental Biology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.affiliation","Schmidt, Julia; \n1\nInstitute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Dreha-Kulaczewski, Steffi; \n2\nDepartment of Pediatics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Zafeiriou, Maria-Patapia; \n3\nInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Schreiber, Marie-Kristin; \n3\nInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Wilken, Bernd; \n6\nDepartment of Pediatric Neurology, Klinikum Kassel, Kassel, Germany"],["dc.contributor.affiliation","Funke, Rudolf; \n6\nDepartment of Pediatric Neurology, Klinikum Kassel, Kassel, Germany"],["dc.contributor.affiliation","Neuhofer, Christiane M; \n1\nInstitute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Altmüller, Janine; \n9\nCologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine, University Hospital Cologne, Cologne, Germany"],["dc.contributor.affiliation","Thiele, Holger; \n9\nCologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine, University Hospital Cologne, Cologne, Germany"],["dc.contributor.affiliation","Nürnberg, Peter; \n9\nCologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine, University Hospital Cologne, Cologne, Germany"],["dc.contributor.affiliation","Biskup, Saskia; \n12\nCeGaT GmbH, Center for Genomics and Transcriptomics, Tübingen, Germany"],["dc.contributor.affiliation","Li, Yun; \n1\nInstitute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Zimmermann, Wolfram Hubertus; \n3\nInstitute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Kaulfuß, Silke; \n1\nInstitute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Yigit, Gökhan; \n1\nInstitute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Wollnik, Bernd; \n1\nInstitute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.author","Schmidt, Julia"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Zafeiriou, Maria Patapia"],["dc.contributor.author","Schreiber, Marie-Kristin"],["dc.contributor.author","Wilken, Bernd"],["dc.contributor.author","Funke, Rudolf"],["dc.contributor.author","Neuhofer, Christiane M"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Biskup, Saskia"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2022-11-30T10:25:07Z"],["dc.date.available","2022-11-30T10:25:07Z"],["dc.date.issued","2022-11-16"],["dc.date.updated","2022-11-30T08:55:41Z"],["dc.description.abstract","STAG2 is a component of the large, evolutionarily highly conserved cohesin complex, which has been linked to various cellular processes like genome organization, DNA replication, gene expression, heterochromatin formation, sister chromatid cohesion, and DNA repair. A wide spectrum of germline variants in genes encoding subunits or regulators of the cohesin complex have previously been identified to cause distinct but phenotypically overlapping multisystem developmental disorders belonging to the group of cohesinopathies. Pathogenic variants in STAG2 have rarely been implicated in an X-linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphic features. Here, we describe for the first time a mosaic STAG2 variant in an individual with developmental delay, microcephaly, and hemihypotrophy of the right side. We characterized the grade of mosaicism by deep sequencing analysis on DNA extracted from EDTA blood, urine and buccal swabs. Furthermore, we report an additional female with a novel de novo splice variant in STAG2. Interestingly, both individuals show supernumerary nipples, a feature that has not been reported associated to STAG2 before. Remarkably, additional analysis of STAG2 transcripts in both individuals showed only wildtype transcripts, even after blockage of nonsense-mediated decay using puromycin in blood lymphocytes. As the phenotype of STAG2-associated cohesinopathies is dominated by global developmental delay, severe microcephaly, and brain abnormalities, we investigated the expression of STAG2 and other related components of the cohesin complex during Bioengineered Neuronal Organoids (BENOs) generation by RNA sequencing. Interestingly, we observed a prominent expression of STAG2, especially between culture days 0 and 15, indicating an essential function of STAG2 in early brain development. In summary, we expand the genotypic and phenotypic spectrum of STAG2-associated cohesinopathies and show that BENOs represent a promising model to gain further insights into the critical role of STAG2 in the complex process of nervous system development."],["dc.identifier.doi","10.3389/fcell.2022.1025332"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117901"],["dc.language.iso","en"],["dc.relation.eissn","2296-634X"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Somatic mosaicism in STAG2-associated cohesinopathies: Expansion of the genotypic and phenotypic spectrum"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Journal of Human Genetics"],["dc.contributor.author","Schmidt, Julia"],["dc.contributor.author","Schreiber, Gudrun"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Funke, Rudolf"],["dc.contributor.author","Wilken, Bernd"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2021-12-01T09:23:16Z"],["dc.date.available","2021-12-01T09:23:16Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Variants in transcription factor p63 have been linked to several autosomal dominantly inherited malformation syndromes. These disorders show overlapping phenotypic characteristics with various combinations of the following features: ectodermal dysplasia, split-hand/foot malformation/syndactyly, lacrimal duct obstruction, hypoplastic breasts and/or nipples, ankyloblepharon filiforme adnatum, hypospadias and cleft lip/palate. We describe a family with six individuals presenting with a striking novel phenotype characterized by a furrowed or cleft tongue, a narrow face, reddish hair, freckles and various foot deformities. Whole-exome sequencing (WES) identified a novel heterozygous variant, c.3G>T, in TP63 affecting the translation initiation codon (p.1Met?). Sanger sequencing confirmed dominant inheritance of this unique variant in all six affected family members. In summary, our findings indicate that heterozygous variants in TP63 affecting the first translation initiation codon result in a novel phenotype dominated by a cleft tongue, expanding the complex genotypic and phenotypic spectrum of TP63 -associated disorders."],["dc.identifier.doi","10.1038/s41431-021-00967-x"],["dc.identifier.pii","967"],["dc.identifier.pmid","34629465"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94604"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/352"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1476-5438"],["dc.relation.issn","1018-4813"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights","CC BY 4.0"],["dc.title","Familial cleft tongue caused by a unique translation initiation codon variant in TP63"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","cge.14174"],["dc.bibliographiccitation.firstpage","239"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Clinical Genetics"],["dc.bibliographiccitation.lastpage","241"],["dc.bibliographiccitation.volume","102"],["dc.contributor.affiliation","Bremmer, Felix; 2\r\nInstitute of Pathology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Brockmann, Knut; 3\r\nInterdisciplinary Pediatric Center for Children With Developmental Disabilities and Severe Chronic Disorders\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Kaulfuß, Silke; 1\r\nInstitute of Human Genetics\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Wollnik, Bernd; 1\r\nInstitute of Human Genetics\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.author","Schmidt, Julia"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2022-07-01T07:35:10Z"],["dc.date.available","2022-07-01T07:35:10Z"],["dc.date.issued","2022"],["dc.date.updated","2022-11-11T13:13:44Z"],["dc.description.abstract","Proteus syndrome is a very rare disorder with progressive, asymmetrical, and disproportionate overgrowth of body parts with a highly variable phenotype. It is associated with mosaicism for the recurrent heterozygous somatic gain-of-function variant c.49G>A (p.Glu17Lys) in the protein kinase AKT1. We report on a girl with a progressive intraosseous lipoma of the frontal bone and additional, nonspecific features including mild developmental delay, strabism, and a limbal dermoid of the left eye. She did not fulfill the criteria for a clinical diagnosis of Proteus syndrome. However, mutation analysis of AKT1 in a lipoma biopsy revealed this specific activating variant. Several cases of progressive intraosseous lipoma of the frontal bone have been reported in the literature. Only in two of these observations, a tentative diagnosis of Proteus syndrome was made, based on additional clinical features, although without molecular-genetic verification. We conclude that oligosymptomatic Proteus syndrome should be considered in progressive intraosseous lipoma, as recognition of this diagnosis has relevant implications for genetic counseling and opens novel treatment options with AKT1 inhibitors rather than surgical procedures."],["dc.description.abstract","We report a case of progressive frontal intraosseous lipoma associated with the specific mosaic AKT1 variant c.49G>A (p.Glu17Lys) and expand the complex phenotypic spectrum of Proteus syndrome.\r\n\r\nimage"],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1111/cge.14174"],["dc.identifier.pmid","35670639"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112102"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/500"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.publisher","Blackwell Publishing Ltd"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1399-0004"],["dc.relation.issn","0009-9163"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","http://creativecommons.org/licenses/by-nc-nd/4.0/"],["dc.title","Progressive frontal intraosseous lipoma: Detection of the mosaic AKT1 variant discloses Proteus 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.artnumber","9"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical and Translational Allergy"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Recke, Andreas"],["dc.contributor.author","Massalme, Elisabeth G."],["dc.contributor.author","Jappe, Uta"],["dc.contributor.author","Steinmüller-Magin, Lars"],["dc.contributor.author","Schmidt, Julia"],["dc.contributor.author","Hellenbroich, Yorck"],["dc.contributor.author","Hüning, Irina"],["dc.contributor.author","Gillessen-Kaesbach, Gabriele"],["dc.contributor.author","Zillikens, Detlef"],["dc.contributor.author","Hartmann, Karin"],["dc.date.accessioned","2019-03-15T10:25:41Z"],["dc.date.available","2019-03-15T10:25:41Z"],["dc.date.issued","2019"],["dc.description.abstract","Hereditary angioedema (HAE) is a life-threatening disease characterized by recurrent episodes of subcutaneous and mucosal swellings and abdominal cramping. Corticosteroids and antihistamines, which are usually beneficial in histamine-induced acquired angioedema, are not effective in HAE. Therefore, diagnosing HAE correctly is crucial for affected patients. We report a family from Northern Germany with six individuals suffering from recurrent swellings, indicating HAE. Laboratory tests and genetic diagnostics of the genes SERPING1, encoding C1 esterase inhibitor (C1-INH), and F12, encoding coagulation factor XII, were unremarkable. In three affected and one yet unaffected member of the family, we were then able to identify the c.988A > G (also termed c.1100A > G) mutation in the plasminogen (PLG) gene, which has recently been described in several families with HAE. This mutation leads to a missense mutation with an amino acid exchange p.Lys330Glu in the kringle 3 domain of plasminogen. There was no direct relationship between the earlier described cases with this mutation and the family we report here. In all affected members of the family, the symptoms manifested in adulthood, with swellings of the face, tongue and larynx, including a fatal case of a 19 year-old female individual. The frequency of the attacks was variable, ranging between once per year to once a month. In one individual, we also found decreased serum levels of plasminogen as well as coagulation factor XII. As previously reported in patients with PLG defects, icatibant proved to be very effective in controlling acute attacks, indicating an involvement of bradykinin in the pathogenesis."],["dc.description.sponsorship","Open Access Publikationsfonds 2019"],["dc.identifier.doi","10.1186/s13601-019-0247-x"],["dc.identifier.pmid","30809376"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15814"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57678"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Identification of the recently described plasminogen gene mutation p.Lys330Glu in a family from Northern Germany with hereditary angioedema"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]