Wollnik, Bernd

[["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.firstpage","975"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","991"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Borchert, Thomas"],["dc.contributor.author","Hübscher, Daniela"],["dc.contributor.author","Guessoum, Celina I."],["dc.contributor.author","Lam, Tuan-Dinh D."],["dc.contributor.author","Ghadri, Jelena R."],["dc.contributor.author","Schellinger, Isabel N."],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Liaw, Norman Y."],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Haas, Jan"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Huber, Mia A."],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Raaz, Uwe"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Lüscher, Thomas F."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Templin, Christian"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.date.accessioned","2018-04-23T11:48:11Z"],["dc.date.available","2018-04-23T11:48:11Z"],["dc.date.issued","2017"],["dc.description.abstract","Background Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. Objectives The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS. Methods Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function. Results Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate–dependent protein kinase A–mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β1-adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function. Conclusions Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype."],["dc.identifier.doi","10.1016/j.jacc.2017.06.061"],["dc.identifier.gro","3142333"],["dc.identifier.pmid","28818208"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16489"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13468"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/204"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation.issn","0735-1097"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.relation.workinggroup","RG Dressel"],["dc.relation.workinggroup","RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Wollnik"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","377"],["dc.bibliographiccitation.issue","06"],["dc.bibliographiccitation.journal","Zeitschrift für Geburtshilfe und Neonatologie"],["dc.bibliographiccitation.lastpage","380"],["dc.bibliographiccitation.volume","224"],["dc.contributor.author","Stromiedel, Helen"],["dc.contributor.author","Van Quekelberghe, Chantal"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Naimi, Ammar Al"],["dc.contributor.author","Bahlmann, Franz"],["dc.contributor.author","Sader, Robert"],["dc.contributor.author","Guchlerner, Marina"],["dc.contributor.author","Lüchtenberg, Marc"],["dc.contributor.author","Latta, Kay"],["dc.contributor.author","Cho, Chie Hee"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Kunzmann, Steffen"],["dc.date.accessioned","2021-04-14T08:23:07Z"],["dc.date.available","2021-04-14T08:23:07Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1055/a-1224-4465"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80801"],["dc.language.iso","de"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1439-1651"],["dc.relation.issn","0948-2393"],["dc.title","Neugeborenes mit Nasenagenesie: Neonatologische Herausforderungen bei der Versorgung eines Neugeborenen mit Bosma-Arhinie-Mikrophthalmie-Syndrom (BAMS)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","416"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurology"],["dc.bibliographiccitation.lastpage","419"],["dc.bibliographiccitation.volume","256"],["dc.contributor.author","Durmaz, Burak"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Cogulu, Ozgur"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Tekgul, Hasan"],["dc.contributor.author","Hazan, Filiz"],["dc.contributor.author","Ozkinay, Ferda"],["dc.date.accessioned","2017-09-07T11:47:34Z"],["dc.date.available","2017-09-07T11:47:34Z"],["dc.date.issued","2009"],["dc.description.abstract","Pontocerebellar hypoplasia (PCH) is a heterogeneous group of disorders characterized by abnormally small cerebellum and brainstem. Recently a rare, novel form of PCH has been reported called cerebellar atrophy with progressive microcephaly (CLAM). Here we report a second family of CLAM with additional phenotypic features and novel molecular findings. Three-year old index patient had severe developmental delay and presented with short stature and microcephaly. Her cranial magnetic resonance imaging revealed hypoplasia of the cerebellum, brainstem and cerebrum associated with hypoplasia of the corpus callosum. Brainstem auditory evoked potentials revealed hearing loss and visual evoked potentials confirmed the optic atrophy. She also had seizures with two posterior epileptic foci on electroencephalogram. Molecular analysis revealed a homozygous haplotype between the markers D7S802 and D7S630 within the originally linked region, narrowing the critical region from 20 Mb to 7 Mb. Two highly relevant candidate genes, CROT and SLC25A40 located in this region were sequenced, but no causative mutations identified. Our case provides additional clinical characteristics on the previously described features of this new entity, and reducing the critical region will now allow systematic positional cloning efforts to identify the causative gene."],["dc.identifier.doi","10.1007/s00415-009-0094-0"],["dc.identifier.gro","3143145"],["dc.identifier.isi","000265732800015"],["dc.identifier.pmid","19277761"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/627"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Dr Dietrich Steinkopff Verlag"],["dc.relation.issn","0340-5354"],["dc.title","Pontocerebellar hypoplasia type III (CLAM): Extended phenotype and novel molecular findings"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","135"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","British Journal of Ophthalmology"],["dc.bibliographiccitation.lastpage","141"],["dc.bibliographiccitation.volume","92"],["dc.contributor.author","Kaplan, Y."],["dc.contributor.author","Vargel, I."],["dc.contributor.author","Kansu, T."],["dc.contributor.author","Akin, B."],["dc.contributor.author","Rohmann, E."],["dc.contributor.author","Kamaci, S."],["dc.contributor.author","Uz, E."],["dc.contributor.author","Ozcelik, T."],["dc.contributor.author","Wollnik, B."],["dc.contributor.author","Akarsu, N. A."],["dc.date.accessioned","2017-09-07T11:48:48Z"],["dc.date.available","2017-09-07T11:48:48Z"],["dc.date.issued","2008"],["dc.description.abstract","Aims: This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family. Methods: Both Xp11 and Xq26 loci were tested by linkage analysis. The 12 exons and intron-exon junctions of the FRMD7 gene were screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme, followed by PCR of the polymorphic CAG repeat of the androgen receptor gene. Results: The family contained 162 individuals, among whom 28 had NYS. Linkage analysis confirmed the Xq26 locus. A novel missense c. 686C > G mutation, which causes the substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) in exon 8 of the FRMD7 gene, was observed. This change was not documented in 120 control individuals. The clinical findings in a female who was homozygous for the mutation were not different from those of affected heterozygous females. Skewed X inactivation was remarkable in the affected females of the family. Conclusions: A novel p. R229G mutation in the FRMD7 gene causes the NYS phenotype, and skewed X inactivation influences the manifestation of the disease in X linked NYS females."],["dc.identifier.doi","10.1136/bjo.2007.128157"],["dc.identifier.gro","3143370"],["dc.identifier.isi","000252054700031"],["dc.identifier.pmid","17962394"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/876"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0007-1161"],["dc.title","Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e10418"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Karner, Courtney M."],["dc.contributor.author","Dietrich, M."],["dc.contributor.author","Johnson, Eric B."],["dc.contributor.author","Kappesser, Natalie"],["dc.contributor.author","Tennert, Christian"],["dc.contributor.author","Percin, E. Ferda"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Carroll, Thomas J."],["dc.contributor.author","Herz, Joachim"],["dc.date.accessioned","2017-09-07T11:46:06Z"],["dc.date.available","2017-09-07T11:46:06Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Development of the kidney is initiated when the ureteric bud (UB) branches from the Wolffian duct and invades the overlying metanephric mesenchyme (MM) triggering the mesenchymal/epithelial interactions that are the basis of organ formation. Multiple signaling pathways must be integrated to ensure proper timing and location of the ureteric bud formation. Methods and Principal Findings: We have used gene targeting to create an Lrp4 null mouse line. The mutation results in early embryonic lethality with a subpenetrant phenotype of kidney agenesis. Ureteric budding is delayed with a failure to stimulate the metanephric mesenchyme in a timely manner, resulting in failure of cellular differentiation and resulting absence of kidney formation in the mouse as well as comparable malformations in humans with Cenani-Lenz syndrome. Conclusion: Lrp4 is a multi-functional receptor implicated in the regulation of several molecular pathways, including Wnt and Bmp signaling. Lrp4(-/-) mice show a delay in ureteric bud formation that results in unilateral or bilateral kidney agenesis. These data indicate that Lrp4 is a critical regulator of UB branching and lack of Lrp4 results in congenital kidney malformations in humans and mice."],["dc.identifier.doi","10.1371/journal.pone.0010418"],["dc.identifier.gro","3142935"],["dc.identifier.isi","000277240100024"],["dc.identifier.pmid","20454682"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/394"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.title","Lrp4 Regulates Initiation of Ureteric Budding and Is Crucial for Kidney Formation - A Mouse Model for Cenani-Lenz Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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","836"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","843"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Moosa, Shahida"],["dc.contributor.author","Yamamoto, Guilherme L."],["dc.contributor.author","Garbes, Lutz"],["dc.contributor.author","Keupp, Katharina"],["dc.contributor.author","Beleza-Meireles, Ana"],["dc.contributor.author","Moreno, Carolina Araujo"],["dc.contributor.author","Valadares, Eugenia Ribeiro"],["dc.contributor.author","de Sousa, Sérgio B."],["dc.contributor.author","Maia, Sofia"],["dc.contributor.author","Saraiva, Jorge"],["dc.contributor.author","Honjo, Rachel S."],["dc.contributor.author","Kim, Chong Ae"],["dc.contributor.author","Cabral de Menezes, Hamilton"],["dc.contributor.author","Lausch, Ekkehart"],["dc.contributor.author","Lorini, Pablo Villavicencio"],["dc.contributor.author","Lamounier, Arsonval"],["dc.contributor.author","Carniero, Tulio Canella Bezerra"],["dc.contributor.author","Giunta, Cecilia"],["dc.contributor.author","Rohrbach, Marianne"],["dc.contributor.author","Janner, Marco"],["dc.contributor.author","Semler, Oliver"],["dc.contributor.author","Beleggia, Filippo"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Reintjes, Nadine"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Cavalcanti, Denise P."],["dc.contributor.author","Zabel, Bernhard"],["dc.contributor.author","Warman, Matthew L."],["dc.contributor.author","Bertola, Debora R."],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Netzer, Christian"],["dc.date.accessioned","2020-12-10T14:22:21Z"],["dc.date.available","2020-12-10T14:22:21Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.ajhg.2019.08.008"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71587"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/19"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG Wollnik"],["dc.title","Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","123"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of the Neurological Sciences"],["dc.bibliographiccitation.lastpage","130"],["dc.bibliographiccitation.volume","246"],["dc.contributor.author","Uyguner, Oya"],["dc.contributor.author","Siva, A"],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Saip, S"],["dc.contributor.author","Altintas, A"],["dc.contributor.author","Apak, M. Y."],["dc.contributor.author","Albayram, S."],["dc.contributor.author","Isik, N."],["dc.contributor.author","Akman-Demir, G"],["dc.contributor.author","Tasyurekli, M"],["dc.contributor.author","Oz, B."],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2017-09-07T11:52:39Z"],["dc.date.available","2017-09-07T11:52:39Z"],["dc.date.issued","2006"],["dc.description.abstract","Mutations in Notch3 gene are responsible for the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). It is a late onset neurological disorder recognized by recurrent strokes and dementia. We describe here the clinical and molecular findings of three unrelated Turkish families with CADASIL syndrome. Two of the families were identified to have the same mutation, p.R110C (c.C328T), located in exon 3 of the Notch3 gene. Interestingly, the phenotypic expression of the disease in these two families was markedly different in severity and age of onset implicating additional genetic and/or non-genetic modulating factors involved in the pathogenesis. In addition, we identified the novel p.C201R (c.T60IC) mutation in exon 4 of the Notch3 gene in a proband of the third family with two consecutive stroke-like episodes and typical MRI findings. Mutations described here cause an odd number of cysteines in the N-terminal of the EGF domain of Notch3 protein, which seems to have an important functional effect in the pathophysiology of CADASIL. The phenotypic variability in families carrying the same molecular defect as presented here makes the prediction of prognosis inconceivable. Although DNA analysis is effective and valuable in diagnosing approximately 90% of the CADASIL patients, lack of genotype-phenotype correlation and prognostic parameters makes the presymptomatic genetic counseling very difficult. (c) 2006 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jns.2006.02.021"],["dc.identifier.gro","3143656"],["dc.identifier.isi","000238625800019"],["dc.identifier.pmid","16730748"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1194"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0022-510X"],["dc.title","The R110C mutation in Notch3 causes variable clinical features in two Turkish families with CADASIL syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6903"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","6912"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Shams, Imad"],["dc.contributor.author","Rohmann, Edyta"],["dc.contributor.author","Eswarakumar, Veraragavan P."],["dc.contributor.author","Lew, Erin D."],["dc.contributor.author","Yuzawa, Satoru"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Schlessinger, Joseph"],["dc.contributor.author","Lax, Irit"],["dc.date.accessioned","2017-09-07T11:49:24Z"],["dc.date.available","2017-09-07T11:49:24Z"],["dc.date.issued","2007"],["dc.description.abstract","Lacrimo-auriculo-dento-digital (LADD) syndrome is characterized by abnormalities in lacrimal and salivary glands, in teeth, and in the distal limbs. Genetic studies have implicated heterozygous mutations in fibroblast growth factor 10 (FGF10) and in FGF receptor 2 (FGFR2) in LADD syndrome. However, it is not clear whether LADD syndrome mutations (LADD mutations) are gain- or loss-of-function mutations. In order to reveal the molecular mechanism underlying LADD syndrome, we have compared the biological properties of FGF10 LADD and FGFR2 LADD mutants to the activities of their normal counterparts. These experiments show that the biological activities of three different FGF10 LADD mutants are severely impaired by different mechanisms. Moreover, haploinsufficiency caused by defective FGF10 mutants leads to LADD syndrome. We also demonstrate that the tyrosine kinase activities of FGFR2 LADD mutants expressed in transfected cells are strongly compromised. Since tyrosine kinase activity is stimulated by ligand-induced receptor dimerization, FGFR2 LADD mutants may also exert a dominant inhibitory effect on signaling via wild-type FGFR2 expressed in the same cell. These experiments underscore the importance of signal strength in mediating biological responses and that relatively small changes in receptor signaling may influence the outcome of developmental processes in cells or organs that do not possess redundant signaling pathway."],["dc.identifier.doi","10.1128/MCB.00544-07"],["dc.identifier.gro","3143431"],["dc.identifier.isi","000249642600027"],["dc.identifier.pmid","17682060"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/944"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NIAMS NIH HHS [R01 AR051886, AR05141448, AR051886, P50 AR054086]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Soc Microbiology"],["dc.relation.issn","0270-7306"],["dc.title","Lacrimo-auricuto-dento-digital syndrome is caused by reduced activity of the fibroblast growth factor 10 (FGF10)-FGF receptor 2 signaling pathwayv"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]