Brockmann, Knut

[["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","2971"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics Part A"],["dc.bibliographiccitation.lastpage","2975"],["dc.bibliographiccitation.volume","182"],["dc.contributor.author","Schröder, Simone"],["dc.contributor.author","Wieland, Britta"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Boltshauser, Eugen"],["dc.contributor.author","Dörk, Thilo"],["dc.contributor.author","Brockmann, Knut"],["dc.date.accessioned","2021-04-14T08:23:43Z"],["dc.date.available","2021-04-14T08:23:43Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Mild clinical phenotypes of ataxia‐telangiectasia (variant A‐T) are associated with biallelic ATM variants resulting in residual function of the ATM kinase. At least one regulatory, missense, or leaky splice site mutation resulting in expression of ATM with low level kinase activity was identified in subjects with variant A‐T. Studies on the pathogenicity of the germline splicing ATM variant c.1066‐6T\\u0026gt;G have provided conflicting results. Using whole‐exome sequencing, we identified two splice site ATM variants, c.1066‐6T\\u0026gt;G; [p.?], and c.2250G\\u0026gt;A, [p.Ile709_Lys750del], in a compound heterozygous state in a 27‐year‐old woman who had been diagnosed as having congenital ocular motor apraxia type Cogan in her childhood. Reappraisal of her clinical phenotype revealed consistency with variant A‐T. Functional analyses showed reduced expression of ATM protein and residual activity of the ATM kinase at a level consistent with variant A‐T. Our results provide evidence for pathogenicity of the leaky ATM splice site variant c.1066‐6T\\u0026gt;G."],["dc.description.sponsorship","Claudia von Schilling Foundation for Breast Cancer Research"],["dc.description.sponsorship","Niedersächsische Ministerium für Wissenschaft und Kultur http://dx.doi.org/10.13039/501100010570"],["dc.identifier.doi","10.1002/ajmg.a.61870"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81021"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","John Wiley \\u0026 Sons, Inc."],["dc.relation.eissn","1552-4833"],["dc.relation.issn","1552-4825"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Evidence of pathogenicity for the leaky splice variant c. 1066‐6T >G in ATM"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","655"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Annals of Clinical and Translational Neurology"],["dc.bibliographiccitation.lastpage","668"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Pringsheim, Milka"],["dc.contributor.author","Mitter, Diana"],["dc.contributor.author","Schröder, Simone"],["dc.contributor.author","Warthemann, Rita"],["dc.contributor.author","Plümacher, Kim"],["dc.contributor.author","Kluger, Gerhard"],["dc.contributor.author","Baethmann, Martina"],["dc.contributor.author","Bast, Thomas"],["dc.contributor.author","Braun, Sarah"],["dc.contributor.author","Büttel, Hans‐Martin"],["dc.contributor.author","Conover, Elizabeth"],["dc.contributor.author","Courage, Carolina"],["dc.contributor.author","Datta, Alexandre N."],["dc.contributor.author","Eger, Angelika"],["dc.contributor.author","Grebe, Theresa A."],["dc.contributor.author","Hasse‐Wittmer, Annette"],["dc.contributor.author","Heruth, Marion"],["dc.contributor.author","Höft, Karen"],["dc.contributor.author","Kaindl, Angela M."],["dc.contributor.author","Karch, Stephanie"],["dc.contributor.author","Kautzky, Torsten"],["dc.contributor.author","Korenke, Georg C."],["dc.contributor.author","Kruse, Bernd"],["dc.contributor.author","Lutz, Richard E."],["dc.contributor.author","Omran, Heymut"],["dc.contributor.author","Patzer, Steffi"],["dc.contributor.author","Philippi, Heike"],["dc.contributor.author","Ramsey, Keri"],["dc.contributor.author","Rating, Tina"],["dc.contributor.author","Rieß, Angelika"],["dc.contributor.author","Schimmel, Mareike"],["dc.contributor.author","Westman, Rachel"],["dc.contributor.author","Zech, Frank‐Martin"],["dc.contributor.author","Zirn, Birgit"],["dc.contributor.author","Ulmke, Pauline A."],["dc.contributor.author","Sokpor, Godwin"],["dc.contributor.author","Tuoc, Tran"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Staudt, Martin"],["dc.contributor.author","Brockmann, Knut"],["dc.date.accessioned","2019-11-25T10:20:06Z"],["dc.date.accessioned","2021-10-27T13:21:31Z"],["dc.date.available","2019-11-25T10:20:06Z"],["dc.date.available","2021-10-27T13:21:31Z"],["dc.date.issued","2019"],["dc.description.abstract","Objective: FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous FOXG1 variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations. Methods: We compiled 34 patients with a heterozygous (likely) pathogenic FOXG1 variant. Qualitative assessment of cerebral anomalies was performed by standardized re-analysis of all 34 MRI data sets. Statistical analysis of genetic, clinical and neuroimaging data were performed. We quantified clinical and neuroimaging phenotypes using severity scores. Telencephalic phenotypes of adult Foxg1+/- mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies. Results: Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner CSF spaces (44%), hypoplasia of basal ganglia (38%), and hypoplasia of frontal lobes (29%). We observed a marked, filiform thinning of the rostrum as recurrent highly typical pattern of corpus callosum anomaly in combination with distinct thickening of the fornix as a characteristic feature. Thickening of the fornices was not reported previously in FOXG1 syndrome. Simplified gyral pattern occurred significantly more frequently in patients with early truncating variants. Higher clinical severity scores were significantly associated with higher neuroimaging severity scores. Modeling of Foxg1 heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix. Interpretation: Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for FOXG1 syndrome."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2019"],["dc.identifier.doi","10.1002/acn3.735"],["dc.identifier.eissn","2328-9503"],["dc.identifier.issn","2328-9503"],["dc.identifier.pmid","31019990"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16705"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92029"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","2328-9503"],["dc.relation.issn","2328-9503"],["dc.relation.issn","2328-9503"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.title","Structural brain anomalies in patients with FOXG 1 syndrome and in Foxg1+/− mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","105012"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.volume","143"],["dc.contributor.author","Lazarov, Elinor"],["dc.contributor.author","Hillebrand, Merle"],["dc.contributor.author","Schröder, Simone"],["dc.contributor.author","Ternka, Katharina"],["dc.contributor.author","Hofhuis, Julia"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Barrantes-Freer, Alonso"],["dc.contributor.author","Pardo, Luis A."],["dc.contributor.author","Fruergaard, Marlene U."],["dc.contributor.author","Nissen, Poul"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Rosewich, Hendrik"],["dc.date.accessioned","2021-04-14T08:23:22Z"],["dc.date.available","2021-04-14T08:23:22Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.nbd.2020.105012"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17488"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80889"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","0969-9961"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Comparative analysis of alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism ATP1A3 mutations reveals functional deficits, which do not correlate with disease severity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]