Brockmann, Knut

[["dc.bibliographiccitation.artnumber","10"],["dc.bibliographiccitation.journal","Molecular Cytogenetics"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Auber, Bernd"],["dc.contributor.author","Bruemmer, Verena"],["dc.contributor.author","Zoll, Barbara"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Boehm, Detlef"],["dc.contributor.author","Liehr, Thomas"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Wilichowski, Ekkehard"],["dc.contributor.author","Argyriou, Loukas"],["dc.contributor.author","Bartels, Iris"],["dc.date.accessioned","2018-11-07T08:35:08Z"],["dc.date.available","2018-11-07T08:35:08Z"],["dc.date.issued","2009"],["dc.description.abstract","Background: Submicroscopic imbalances in the subtelomeric regions of the chromosomes are considered to play an important role in the aetiology of mental retardation (MR). The aim of the study was to evaluate a quantitative PCR (qPCR) protocol established by Boehm et al. (2004) in the clinical routine of subtelomeric testing. Results: 296 patients with MR and a normal karyotype (500-550 bands) were screened for subtelomeric imbalances by using qPCR combined with SYBR green detection. In total, 17 patients (5.8%) with 20 subtelomeric imbalances were identified. Six of the aberrations (2%) were classified as causative for the symptoms, because they occurred either de novo in the patients (5 cases) or the aberration were be detected in the patient and an equally affected parent (1 case). The extent of the deletions ranged from 1.8 to approximately 10 Mb, duplications were 1.8 to approximately 5 Mb in size. In 6 patients, the copy number variations (CNVs) were rated as benign polymorphisms, and the clinical relevance of these CNVs remains unclear in 5 patients (1.7%). Therefore, the overall frequency of clinically relevant imbalances ranges between 2% and 3.7% in our cohort."],["dc.identifier.doi","10.1186/1755-8166-2-10"],["dc.identifier.isi","000208460900009"],["dc.identifier.pmid","19284615"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5765"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17987"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1755-8166"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Identification of subtelomeric genomic imbalances and breakpoint mapping with quantitative PCR in 296 individuals with congenital defects and/or mental retardation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","64"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Orphanet Journal of Rare Diseases"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Reinert, Marie-Christine"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Catarino, Claudia B."],["dc.contributor.author","Klopstock, Thomas"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Schittkowski, Michael Peter"],["dc.contributor.author","Wilichowski, Ekkehard"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Brockmann, Knut"],["dc.date.accessioned","2021-04-14T08:28:08Z"],["dc.date.available","2021-04-14T08:28:08Z"],["dc.date.issued","2021"],["dc.date.updated","2022-07-29T12:17:42Z"],["dc.description.abstract","Background Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and characterized by acute or subacute painless visual loss. Environmental factors reported to trigger visual loss in LHON mutation carriers include smoking, heavy intake of alcohol, raised intraocular pressure, and some drugs, including several carbonic anhydrase inhibitors. The antiepileptic drug sulthiame (STM) is effective especially in focal seizures, particularly in benign epilepsy of childhood with centrotemporal spikes, and widely used in pediatric epileptology. STM is a sulfonamide derivate and an inhibitor of mammalian carbonic anhydrase isoforms I–XIV. Results We describe two unrelated patients, an 8-year-old girl and an 11-year-old boy, with cryptogenic focal epilepsy, who suffered binocular (subject #1) or monocular (subject #2) visual loss in close temporal connection with starting antiepileptic pharmacotherapy with STM. In both subjects, visual loss was due to LHON. We used real-time respirometry in fibroblasts derived from LHON patients carrying the same mitochondrial mutations as our two subjects to investigate the effect of STM on oxidative phosphorylation. Oxygen consumption rate in fibroblasts from a healthy control was not impaired by STM compared with a vehicle control. In contrast, fibroblasts carrying the m.14484T>C or the m.3460G>A LHON mutation displayed a drastic reduction of the respiration rate when treated with STM compared to vehicle control. Conclusions Our observations point to a causal relationship between STM treatment and onset or worsening of visual failure in two subjects with LHON rather than pure coincidence. We conclude that antiepileptic medication with STM may pose a risk for visual loss in LHON mutation carriers and should be avoided in these patients."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.citation","Orphanet Journal of Rare Diseases. 2021 Feb 04;16(1):64"],["dc.identifier.doi","10.1186/s13023-021-01690-y"],["dc.identifier.pmid","33541401"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17726"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82509"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/219"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/102"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | A06: Mitochondrienfunktion und -umsatz in Synapsen"],["dc.relation.eissn","1750-1172"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","Sulthiame"],["dc.subject","Carbonic anhydrase inhibitor"],["dc.subject","Adverse effects"],["dc.subject","Leber hereditary optic neuropathy"],["dc.subject","LHON"],["dc.subject","Oxygen consumption rate"],["dc.title","Sulthiame impairs mitochondrial function in vitro and may trigger onset of visual loss in Leber hereditary optic neuropathy"],["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","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","764"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","The Lancet Neurology"],["dc.bibliographiccitation.lastpage","773"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Rosewich, Hendrik"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Ohlenbusch, Andreas"],["dc.contributor.author","Maschke, Ulrike"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Frommolt, Peter"],["dc.contributor.author","Zim, Birgit"],["dc.contributor.author","Ebinger, Friedrich"],["dc.contributor.author","Siemes, Hartmut"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:48:26Z"],["dc.date.available","2017-09-07T11:48:26Z"],["dc.date.issued","2012"],["dc.description.abstract","Background Alternating hemiplegia of childhood (AHC) is a rare neurological disorder characterised by early-onset episodes of hemiplegia, dystonia, various paroxysmal symptoms, and developmental impairment. Almost all cases of AHC are sporadic but AHC concordance in monozygotic twins and dominant transmission in a family with a milder phenotype have been reported. Thus, we aimed to identify de-novo mutations associated with this disease. Methods We recruited patients with clinically characterised AHC from paediatric neurology departments in Germany and with the aid of a parental support group between Sept, 2004, and May 18, 2012. We used whole-exome sequencing of three proband-parent trios to identify a disease-associated gene and then tested whether mutations in the gene were also present in the remaining patients and their healthy parents. We analysed genotypes and characterised their associations with the phenotypic spectrum of the disease. Findings We studied 15 female and nine male patients with AHC who were aged 8-35 years. ATP1A3 emerged as the disease-associated gene in AHC. Whole-exome sequencing showed three heterozygous de-novo missense mutations. Sequencing of the 21 remaining affected individuals identified disease-associated mutations in ATP1A3 in all patients, including six de-novo missense mutations and one de-novo splice-site mutation. Because ATP1A3 is also the gene associated with rapid-onset dystonia-parkinsonism (DYT12, OMIM 128235) we compared the genotypes and phenotypes of patients with AHC in our cohort with those of patients with rapid-onset dystonia-parkinsonism reported in the scientific literature. We noted overlapping clinical features, such as abrupt onset of dystonic episodes often triggered by emotional stress, a rostrocaudal (face to arm to leg) gradient of involvement, and signs of brainstem dysfunction, as well as clearly differentiating clinical characteristics, such as episodic hemiplegia and quadriplegia. Interpretation Mutation analysis of the ATP1A3 gene in patients who met clinical criteria for AHC allows for definite genetic diagnosis and sound genetic counselling. AHC and rapid-onset dystonia-parkinsonism are allelic diseases related to mutations in ATP1A3 and form a phenotypical continuum of a dystonic movement disorder."],["dc.identifier.doi","10.1016/S1474-4422(12)70182-5"],["dc.identifier.gro","3142472"],["dc.identifier.isi","000307911700011"],["dc.identifier.pmid","22850527"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11305"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8662"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Eva Luise and Horst Kohler Foundation for Humans with Rare Diseases"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Inc"],["dc.relation.eissn","1474-4465"],["dc.relation.issn","1474-4422"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","74"],["dc.bibliographiccitation.journal","Molecular Cytogenetics"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Schwaibold, Eva Maria Christina"],["dc.contributor.author","Smogavec, Mateja"],["dc.contributor.author","Hobbiebrunken, Elke"],["dc.contributor.author","Winter, Lorenz"],["dc.contributor.author","Zoll, Barbara"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Pauli, Silke"],["dc.date.accessioned","2018-11-07T09:33:25Z"],["dc.date.available","2018-11-07T09:33:25Z"],["dc.date.issued","2014"],["dc.description.abstract","Background: Kleefstra syndrome is characterized by intellectual disability, muscular hypotonia in childhood and typical facial features. It results from either a microdeletion of or a deleterious sequence variant in the gene euchromatic histone-lysine N-methyltransferase 1 (EHMT1) on chromosome 9q34. Results: We report on a 3-year-old girl with characteristic symptoms of Kleefstra syndrome. Array comparative genomic hybridization analysis revealed a 145 kilobases duplication spanning exons 2 to 10 of EHMT1. Sequence analysis characterized it as an intragenic tandem duplication leading to a frame shift with a premature stop codon in EHMT1. Conclusions: This is the first description of an intragenic duplication of EHMT1 resulting in Kleefstra syndrome."],["dc.identifier.doi","10.1186/s13039-014-0074-7"],["dc.identifier.isi","000344120100001"],["dc.identifier.pmid","25349628"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11004"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31961"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1755-8166"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Intragenic duplication of EHMT1 gene results in Kleefstra syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Huang, Jianying"],["dc.contributor.author","Estacion, Mark"],["dc.contributor.author","Zhao, Peng"],["dc.contributor.author","Dib-Hajj, Fadia B."],["dc.contributor.author","Schulman, Betsy"],["dc.contributor.author","Abicht, Angela"],["dc.contributor.author","Kurth, Ingo"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Waxman, Stephen G."],["dc.contributor.author","Dib-Hajj, Sulayman D."],["dc.date.accessioned","2020-12-10T18:44:34Z"],["dc.date.available","2020-12-10T18:44:34Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.3389/fnins.2019.00918"],["dc.identifier.eissn","1662-453X"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16776"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78510"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A Novel Gain-of-Function Nav1.9 Mutation in a Child With Episodic Pain"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","549"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Medical Genetics"],["dc.bibliographiccitation.lastpage","553"],["dc.bibliographiccitation.volume","59"],["dc.contributor.affiliation","Yigit, Gökhan; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Sheffer, Ruth; \r\n2\r\nDepartment of Human Genetics, Hadassah University Hospital, Jerusalem, Israel"],["dc.contributor.affiliation","Daana, Muhannad; \r\n3\r\nChild Development Institute, Clalit Health Services, Tel Aviv, Israel"],["dc.contributor.affiliation","Li, Yun; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Kaygusuz, Emrah; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Mor-Shakad, Hagar; \r\n2\r\nDepartment of Human Genetics, Hadassah University Hospital, Jerusalem, Israel"],["dc.contributor.affiliation","Altmüller, Janine; \r\n5\r\nCologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany"],["dc.contributor.affiliation","Nürnberg, Peter; \r\n5\r\nCologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany"],["dc.contributor.affiliation","Douiev, Liza; \r\n2\r\nDepartment of Human Genetics, Hadassah University Hospital, Jerusalem, Israel"],["dc.contributor.affiliation","Kaulfuss, Silke; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Burfeind, Peter; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Wollnik, Bernd; \r\n1\r\nInstitute of Human Genetics, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.affiliation","Brockmann, Knut; \r\n7\r\nInterdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, University Medical Center Göttingen, Gottingen, Germany"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Sheffer, Ruth"],["dc.contributor.author","Daana, Muhannad"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Kaygusuz, Emrah"],["dc.contributor.author","Mor-Shakad, Hagar"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Douiev, Liza"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Kaulfuss, Silke"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2021-07-05T14:57:45Z"],["dc.date.available","2021-07-05T14:57:45Z"],["dc.date.issued","2021"],["dc.date.updated","2022-05-21T14:18:33Z"],["dc.description.abstract","Background Developmental and epileptic encephalopathies (DEEs) represent a group of severe neurological disorders characterised by an onset of refractory seizures during infancy or early childhood accompanied by psychomotor developmental delay or regression. DEEs are genetically heterogeneous with, to date, more than 80 different genetic subtypes including DEE31 caused by heterozygous missense variants in DNM1 . Methods We performed a detailed clinical characterisation of two unrelated patients with DEE and used whole-exome sequencing to identify causative variants in these individuals. The identified variants were tested for cosegregation in the respective families. Results We excluded pathogenic variants in known, DEE-associated genes. We identified homozygous nonsense variants, c.97C>T; p.(Gln33 ) in family 1 and c.850C>T; p.(Gln284 ) in family 2, in the DNM1 gene, indicating that biallelic, loss-of-function pathogenic variants in DNM1 cause DEE. Conclusion Our finding that homozygous, loss-of-function variants in DNM1 cause DEE expands the spectrum of pathogenic variants in DNM1 . All parents who were heterozygous carriers of the identified loss-of-function variants were healthy and did not show any clinical symptoms, indicating that the type of mutation in DNM1 determines the pattern of inheritance."],["dc.description.abstract","Background Developmental and epileptic encephalopathies (DEEs) represent a group of severe neurological disorders characterised by an onset of refractory seizures during infancy or early childhood accompanied by psychomotor developmental delay or regression. DEEs are genetically heterogeneous with, to date, more than 80 different genetic subtypes including DEE31 caused by heterozygous missense variants in DNM1 . Methods We performed a detailed clinical characterisation of two unrelated patients with DEE and used whole-exome sequencing to identify causative variants in these individuals. The identified variants were tested for cosegregation in the respective families. Results We excluded pathogenic variants in known, DEE-associated genes. We identified homozygous nonsense variants, c.97C>T; p.(Gln33 ) in family 1 and c.850C>T; p.(Gln284 ) in family 2, in the DNM1 gene, indicating that biallelic, loss-of-function pathogenic variants in DNM1 cause DEE. Conclusion Our finding that homozygous, loss-of-function variants in DNM1 cause DEE expands the spectrum of pathogenic variants in DNM1 . All parents who were heterozygous carriers of the identified loss-of-function variants were healthy and did not show any clinical symptoms, indicating that the type of mutation in DNM1 determines the pattern of inheritance."],["dc.identifier","34172529"],["dc.identifier.doi","10.1136/jmedgenet-2021-107769"],["dc.identifier.pmid","34172529"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87729"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/396"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/311"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-441"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation.eissn","1468-6244"],["dc.relation.issn","0022-2593"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights.uri","http://creativecommons.org/licenses/by-nc/4.0/"],["dc.title","Loss-of-function variants in DNM1 cause a specific form of developmental and epileptic encephalopathy only in biallelic state"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","570"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","American Journal of Medical Genetics. Part A"],["dc.bibliographiccitation.lastpage","575"],["dc.bibliographiccitation.volume","182"],["dc.contributor.author","Koehler, Katrin"],["dc.contributor.author","Schuelke, Markus"],["dc.contributor.author","Hell, Anna K."],["dc.contributor.author","Huebner, Angela"],["dc.contributor.author","Schittkowski, Michael"],["dc.contributor.author","Brockmann, Knut"],["dc.date.accessioned","2020-06-15T15:13:11Z"],["dc.date.available","2020-06-15T15:13:11Z"],["dc.date.issued","2020"],["dc.description.abstract","Cohen syndrome (CS) is a rare autosomal recessive disorder associated with mutations in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. The core clinical phenotype comprises a characteristic facial gestalt, marked developmental delay, and myopia. Additional, nonobligatory features include obesity, microcephaly, short stature, muscular hypotonia, scoliosis, narrow hands and feet, progressive retinopathy, as well as neutropenia. Here we report a novel homozygous nonsense mutation in the VPS13B gene and previously undescribed clinical features in a 19-year-old woman with developmental delay, intellectual disability, and a particular facial appearance. The patient showed several features consistent with CS. In addition, the parents observed congenital alacrima and anhidrosis persisting until onset of puberty. The diagnosis was not established based on the clinical phenotype. We performed whole-genome sequencing and identified a novel homozygous nonsense mutation c.62T>G (NM_152564.4), p.(Leu21 ) in the VPS13B gene. Our findings extended the previously reported phenotype of CS. We conclude that transient, prepubertal alacrima and anhidrosis are part of the phenotypic spectrum of CS associated with a novel homozygous nonsense mutation in the VPS13B gene."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG) http://dx.doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1002/ajmg.a.61435"],["dc.identifier.pmid","31825161"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17057"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66329"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","John Wiley \\u0026 Sons, Inc."],["dc.relation.eissn","1552-4833"],["dc.relation.issn","1552-4825"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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","77"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurology"],["dc.bibliographiccitation.lastpage","85"],["dc.bibliographiccitation.volume","87"],["dc.contributor.author","Balestrini, Simona"],["dc.contributor.author","Milh, Mathieu"],["dc.contributor.author","Castiglioni, Claudia"],["dc.contributor.author","Lüthy, Kevin"],["dc.contributor.author","Finelli, Mattea J."],["dc.contributor.author","Verstreken, Patrik"],["dc.contributor.author","Cardon, Aaron"],["dc.contributor.author","Stražišar, Barbara Gnidovec"],["dc.contributor.author","Holder, J. Lloyd"],["dc.contributor.author","Lesca, Gaetan"],["dc.contributor.author","Mancardi, Maria M."],["dc.contributor.author","Poulat, Anne L."],["dc.contributor.author","Repetto, Gabriela M."],["dc.contributor.author","Banka, Siddharth"],["dc.contributor.author","Bilo, Leonilda"],["dc.contributor.author","Birkeland, Laura E."],["dc.contributor.author","Bosch, Friedrich"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Cross, J. Helen"],["dc.contributor.author","Doummar, Diane"],["dc.contributor.author","Félix, Temis M."],["dc.contributor.author","Giuliano, Fabienne"],["dc.contributor.author","Hori, Mutsuki"],["dc.contributor.author","Hüning, Irina"],["dc.contributor.author","Kayserili, Hulia"],["dc.contributor.author","Kini, Usha"],["dc.contributor.author","Lees, Melissa M."],["dc.contributor.author","Meenakshi, Girish"],["dc.contributor.author","Mewasingh, Leena"],["dc.contributor.author","Pagnamenta, Alistair T."],["dc.contributor.author","Peluso, Silvio"],["dc.contributor.author","Mey, Antje"],["dc.contributor.author","Rice, Gregory M."],["dc.contributor.author","Rosenfeld, Jill A."],["dc.contributor.author","Taylor, Jenny C."],["dc.contributor.author","Troester, Matthew M."],["dc.contributor.author","Stanley, Christine M."],["dc.contributor.author","Ville, Dorothee"],["dc.contributor.author","Walkiewicz, Magdalena"],["dc.contributor.author","Falace, Antonio"],["dc.contributor.author","Fassio, Anna"],["dc.contributor.author","Lemke, Johannes R."],["dc.contributor.author","Biskup, Saskia"],["dc.contributor.author","Tardif, Jessica"],["dc.contributor.author","Ajeawung, Norbert F."],["dc.contributor.author","Tolun, Aslihan"],["dc.contributor.author","Corbett, Mark"],["dc.contributor.author","Gecz, Jozef"],["dc.contributor.author","Afawi, Zaid"],["dc.contributor.author","Howell, Katherine B."],["dc.contributor.author","Oliver, Karen L."],["dc.contributor.author","Berkovic, Samuel F."],["dc.contributor.author","Scheffer, Ingrid E."],["dc.contributor.author","de Falco, Fabrizio A."],["dc.contributor.author","Oliver, Peter L."],["dc.contributor.author","Striano, Pasquale"],["dc.contributor.author","Zara, Federico"],["dc.contributor.author","Campeau, Phillipe M."],["dc.contributor.author","Sisodiya, S.M."],["dc.date.accessioned","2020-12-10T18:41:43Z"],["dc.date.available","2020-12-10T18:41:43Z"],["dc.date.issued","2016"],["dc.description.abstract","Objective:To evaluate the phenotypic spectrum associated with mutations in TBC1D24.Methods:We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24).Results:Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function.Conclusions:TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes."],["dc.identifier.doi","10.1212/WNL.0000000000002807"],["dc.identifier.eissn","1526-632X"],["dc.identifier.isi","000380107300019"],["dc.identifier.issn","0028-3878"],["dc.identifier.pmid","27281533"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13550"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77656"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1526-632X"],["dc.relation.issn","0028-3878"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]