Dreha-Kulaczewski, Steffi F.

[["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.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.artnumber","818"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Weissbach, Susann"],["dc.contributor.author","Church, Joseph A."],["dc.contributor.author","Schnur, Rhonda"],["dc.contributor.author","Krusen, Martina"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Kühn-Velten, W. Nikolaus"],["dc.contributor.author","Wolf, Annika"],["dc.contributor.author","Huppke, Brenda"],["dc.contributor.author","Millan, Francisca"],["dc.contributor.author","Begtrup, Amber"],["dc.contributor.author","Almusafri, Fatima"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Müller, Michael"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2018-04-23T11:47:26Z"],["dc.date.available","2018-04-23T11:47:26Z"],["dc.date.issued","2017"],["dc.description.abstract","Transcription factor NRF2, encoded by NFE2L2, is the master regulator of defense against stress in mammalian cells. Somatic mutations of NFE2L2 leading to NRF2 accumulation promote cell survival and drug resistance in cancer cells. Here we show that the same mutations as inborn de novo mutations cause an early onset multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms. NRF2 accumulation leads to widespread misregulation of gene expression and an imbalance in cytosolic redox balance. The unique combination of white matter lesions, hypohomocysteinaemia and increased G-6-P-dehydrogenase activity will facilitate early diagnosis and therapeutic intervention of this novel disorder."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1038/s41467-017-00932-7"],["dc.identifier.gro","3142218"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14817"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13340"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]