Kornak, Uwe

[["dc.contributor.author","Yang, Haisheng"],["dc.contributor.author","Seliger, Anne"],["dc.contributor.author","Thelen, Michael"],["dc.contributor.author","Chan, Wing-Lee"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Willie, Bettina"],["dc.date.accessioned","2020-06-19T10:10:08Z"],["dc.date.available","2020-06-19T10:10:08Z"],["dc.date.issued","2017"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66558"],["dc.title","Altered Bone Formation Response to Mechanical Loading in a Mouse Model of the Progeroid Disorder Gerodermia Osteodysplastica"],["dc.type","report"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","508"],["dc.bibliographiccitation.journal","Indian Journal of Medical Research"],["dc.bibliographiccitation.lastpage","514"],["dc.bibliographiccitation.volume","131"],["dc.contributor.author","Phadke, Shubha"],["dc.contributor.author","Fischer-Zirnsak, Björn"],["dc.contributor.author","Gupta, Neerja"],["dc.contributor.author","Ranganath, Prajnya"],["dc.contributor.author","Kabra, Madhulika"],["dc.contributor.author","Kornak, Uwe"],["dc.date.accessioned","2020-06-19T09:36:11Z"],["dc.date.available","2020-06-19T09:36:11Z"],["dc.date.issued","2010"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66533"],["dc.title","Novel mutations in Indian patients with autosomal recessive infantile malignant osteopetrosis"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","512"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Revue du Rhumatisme"],["dc.bibliographiccitation.lastpage","518"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Kornak, Uwe"],["dc.date.accessioned","2020-06-23T14:52:17Z"],["dc.date.available","2020-06-23T14:52:17Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1016/j.rhum.2011.09.005"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66670"],["dc.relation.issn","1169-8330"],["dc.title","Modèles animaux avec phénotypes pathologiques de minéralisation"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","127"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Witkos, Tomasz M"],["dc.contributor.author","Chan, Wing Lee"],["dc.contributor.author","Joensuu, Merja"],["dc.contributor.author","Rhiel, Manuel"],["dc.contributor.author","Pallister, Ed"],["dc.contributor.author","Thomas-Oates, Jane"],["dc.contributor.author","Mould, A Paul"],["dc.contributor.author","Mironov, Alex A"],["dc.contributor.author","Biot, Christophe"],["dc.contributor.author","Guerardel, Yann"],["dc.contributor.author","Morelle, Willy"],["dc.contributor.author","Ungar, Daniel"],["dc.contributor.author","Wieland, Felix T"],["dc.contributor.author","Jokitalo, Eija"],["dc.contributor.author","Tassabehji, May"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Lowe, Martin"],["dc.date.accessioned","2020-06-23T14:53:55Z"],["dc.date.available","2020-06-23T14:53:55Z"],["dc.date.issued","2019"],["dc.description.abstract","COPI is a key mediator of protein trafficking within the secretory pathway. COPI is recruited to the membrane primarily through binding to Arf GTPases, upon which it undergoes assembly to form coated transport intermediates responsible for trafficking numerous proteins, including Golgi-resident enzymes. Here, we identify GORAB, the protein mutated in the skin and bone disorder gerodermia osteodysplastica, as a component of the COPI machinery. GORAB forms stable domains at the trans-Golgi that, via interactions with the COPI-binding protein Scyl1, promote COPI recruitment to these domains. Pathogenic GORAB mutations perturb Scyl1 binding or GORAB assembly into domains, indicating the importance of these interactions. Loss of GORAB causes impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor, and support the view that defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica."],["dc.identifier.doi","10.1038/s41467-018-08044-6"],["dc.identifier.pmid","30631079"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66690"],["dc.language.iso","en"],["dc.relation.issn","2041-1723"],["dc.title","GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","334"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Osteoarthritis and Cartilage"],["dc.bibliographiccitation.lastpage","343"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Rolvien, T"],["dc.contributor.author","Yorgan, T A"],["dc.contributor.author","Kornak, U."],["dc.contributor.author","Hermans-Borgmeyer, I"],["dc.contributor.author","Mundlos, S"],["dc.contributor.author","Schmidt, T"],["dc.contributor.author","Niemeier, A"],["dc.contributor.author","Schinke, T"],["dc.contributor.author","Amling, M"],["dc.contributor.author","Oheim, R"],["dc.date.accessioned","2020-06-23T14:52:08Z"],["dc.date.available","2020-06-23T14:52:08Z"],["dc.date.issued","2020"],["dc.description.abstract","Spondyloepiphyseal dysplasia, a combination of progressive arthropathy with variable signs of skeletal dysplasia, can be a result of mutations in the collagen, type II, alpha 1 (COL2A1) gene. However, the bone involvement (e.g., density, microstructure) in this disorder has hitherto not been studied."],["dc.identifier.doi","10.1016/j.joca.2019.12.011"],["dc.identifier.pmid","31958497"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66668"],["dc.language.iso","en"],["dc.relation.eissn","1522-9653"],["dc.relation.issn","1063-4584"],["dc.title","Skeletal deterioration in COL2A1-related spondyloepiphyseal dysplasia occurs prior to osteoarthritis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","161"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Archives of Biochemistry and Biophysics"],["dc.bibliographiccitation.lastpage","165"],["dc.bibliographiccitation.volume","473"],["dc.contributor.author","Supanchart, Chayarop"],["dc.contributor.author","Kornak, Uwe"],["dc.date.accessioned","2020-06-19T10:26:21Z"],["dc.date.available","2020-06-19T10:26:21Z"],["dc.date.issued","2008-05-15"],["dc.description.abstract","The resorbing osteoclast is an exceptional cell that secretes large amounts of acid through the coupled activity of a v-type H+-ATPase and a chloride channel that both reside in the ruffled membrane. Impairment of this acid secretion machinery by genetic mutations can abolish bone resorption activity, resulting in osteopetrotic phenotypes. Another key feature of osteoclasts is the transport of high amounts of calcium and phosphate from the resorption lacuna to the basolateral plasma membrane. Evidence exists that this occurs in part through entry of these ions into the osteoclast cytosol. Handling of such large amounts of a cellular messenger requires elaborate mechanisms. Membrane proteins that regulate osteoclast calcium homeostasis and the effect of calcium on osteoclast function and survival are therefore the second main focus of this review."],["dc.identifier.doi","10.1016/j.abb.2008.03.029"],["dc.identifier.pmid","18406337"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66565"],["dc.language.iso","en"],["dc.relation.eissn","1096-0384"],["dc.relation.issn","0003-9861"],["dc.title","Ion channels and transporters in osteoclasts"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Iranian Journal of Pediatrics"],["dc.contributor.author","Malakan Rad, Elaheh"],["dc.contributor.author","Zeinaloo, Ali-Akbar"],["dc.contributor.author","Kariminejad, Ariana"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Fischer-Zirnsak, Bjorn"],["dc.contributor.author","Mohamadpour, Masoud"],["dc.date.accessioned","2020-06-19T10:26:43Z"],["dc.date.available","2020-06-19T10:26:43Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.5812/ijp.6135"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66569"],["dc.relation.issn","2008-2142"],["dc.relation.issn","2008-2150"],["dc.title","Novel FBLN5 Mutation of Congenital Autosomal Recessive Cutis Laxa With Isolated Right Ventricular Non-Compaction (RVNC): New Findings on Echocardiographic Speckle-Tracking Strain Imaging of RVNC"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","325"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","328"],["dc.bibliographiccitation.volume","62"],["dc.contributor.author","Al-Bughaili, Mohammed"],["dc.contributor.author","Neuhann, Teresa M"],["dc.contributor.author","Flöttmann, Ricarda"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Spielmann, Malte"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Fischer-Zirnsak, Björn"],["dc.date.accessioned","2020-06-23T14:53:14Z"],["dc.date.available","2020-06-23T14:53:14Z"],["dc.date.issued","2017-02"],["dc.description.abstract","Gerodermia osteodysplastica is a recessive segmental progeroid disorder mainly characterized by wrinkled skin, generalized connective tissue weakness, infantile onset osteoporosis and normal intelligence. Coding mutations in GORAB, localized on chromosome 1q24.2, are the cause of this disease. 1q24 deletions underlie a spectrum of disorders with intellectual disability and ear abnormalities as phenotypic hallmarks. Here we report on an individual from Azerbaijan originating from a non-consanguineous couple showing short stature, cutis laxa, frequent fractures, facial dysmorphism, cup-shaped ears and intellectual disability. Sanger sequencing of GORAB revealed the seemingly homozygous missense mutation p.Ser175Phe. This mutation was detected in a heterozygous state in the clinically unaffected mother, but was absent in the healthy father. We performed copy-number investigations by high-resolution array-CGH and PCR approaches and found an ~6 Mb de novo deletion spanning 1q23.3-q24.2 in the affected boy. This novel combination of genetic defects very well explains the phenotype that goes beyond the usual presentation of gerodermia osteodysplastica. Our data provide new insight into the phenotypic spectrum of 1q23-q25 deletions and shows that the combination with another pathogenic allele can lead to more severe clinical manifestations."],["dc.identifier.doi","10.1038/jhg.2016.111"],["dc.identifier.pmid","27604556"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66682"],["dc.language.iso","en"],["dc.relation.eissn","1435-232X"],["dc.relation.issn","1434-5161"],["dc.title","A de novo 1q23.3-q24.2 deletion combined with a GORAB missense mutation causes a distinctive phenotype with cutis laxa"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2149"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","2165"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Hucthagowder, Vishwanathan"],["dc.contributor.author","Morava, Eva"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Lefeber, Dirk J"],["dc.contributor.author","Fischer, Björn"],["dc.contributor.author","Dimopoulou, Aikaterini"],["dc.contributor.author","Aldinger, Annika"],["dc.contributor.author","Choi, Jiwon"],["dc.contributor.author","Davis, Elaine C"],["dc.contributor.author","Abuelo, Dianne N"],["dc.contributor.author","Adamowicz, Maciej"],["dc.contributor.author","Al-Aama, Jumana"],["dc.contributor.author","Basel-Vanagaite, Lina"],["dc.contributor.author","Fernandez, Bridget"],["dc.contributor.author","Greally, Marie T"],["dc.contributor.author","Gillessen-Kaesbach, Gabriele"],["dc.contributor.author","Kayserili, Hulya"],["dc.contributor.author","Lemyre, Emmanuelle"],["dc.contributor.author","Tekin, Mustafa"],["dc.contributor.author","Türkmen, Seval"],["dc.contributor.author","Tuysuz, Beyhan"],["dc.contributor.author","Yüksel-Konuk, Berrin"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Van Maldergem, Lionel"],["dc.contributor.author","Wevers, Ron A"],["dc.contributor.author","Urban, Zsolt"],["dc.date.accessioned","2020-06-24T12:24:09Z"],["dc.date.available","2020-06-24T12:24:09Z"],["dc.date.issued","2009-06-15"],["dc.description.abstract","Autosomal recessive cutis laxa type 2 (ARCL2), a syndrome of growth and developmental delay and redundant, inelastic skin, is caused by mutations in the a2 subunit of the vesicular ATPase H+-pump (ATP6V0A2). The goal of this study was to define the disease mechanisms that lead to connective tissue lesions in ARCL2. In a new cohort of 17 patients, DNA sequencing of ATP6V0A2 detected either homozygous or compound heterozygous mutations. Considerable allelic and phenotypic heterogeneity was observed, with a missense mutation of a moderately conserved residue p.P87L leading to unusually mild disease. Abnormal N- and/or mucin type O-glycosylation was observed in all patients tested. Premature stop codon mutations led to decreased ATP6V0A2 mRNA levels by destabilizing the mutant mRNA via the nonsense-mediated decay pathway. Loss of ATP6V0A2 either by siRNA knockdown or in ARCL2 cells resulted in distended Golgi cisternae, accumulation of abnormal lysosomes and multivesicular bodies. Immunostaining of ARCL2 cells showed the accumulation of tropoelastin (TE) in the Golgi and in large, abnormal intracellular and extracellular aggregates. Pulse-chase studies confirmed impaired secretion and increased intracellular retention of TE, and insoluble elastin assays showed significantly reduced extracellular deposition of mature elastin. Fibrillin-1 microfibril assembly and secreted lysyl oxidase activity were normal in ARCL2 cells. TUNEL staining demonstrated increased rates of apoptosis in ARCL2 cell cultures. We conclude that loss-of-function mutations in ATP6V0A2 lead to TE aggregation in the Golgi, impaired clearance of TE aggregates and increased apoptosis of elastogenic cells."],["dc.identifier.doi","10.1093/hmg/ddp148"],["dc.identifier.pmid","19321599"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66712"],["dc.language.iso","en"],["dc.relation.eissn","1460-2083"],["dc.relation.issn","0964-6906"],["dc.title","Loss-of-function mutations in ATP6V0A2 impair vesicular trafficking, tropoelastin secretion and cell survival"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","631"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","639"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Fischer-Zirnsak, Björn"],["dc.contributor.author","Segebrecht, Lara"],["dc.contributor.author","Schubach, Max"],["dc.contributor.author","Charles, Perrine"],["dc.contributor.author","Alderman, Emily"],["dc.contributor.author","Brown, Kathleen"],["dc.contributor.author","Cadieux-Dion, Maxime"],["dc.contributor.author","Cartwright, Tracy"],["dc.contributor.author","Chen, Yanmin"],["dc.contributor.author","Costin, Carrie"],["dc.contributor.author","Fehr, Sarah"],["dc.contributor.author","Fitzgerald, Keely M"],["dc.contributor.author","Fleming, Emily"],["dc.contributor.author","Foss, Kimberly"],["dc.contributor.author","Ha, Thoa"],["dc.contributor.author","Hildebrand, Gabriele"],["dc.contributor.author","Horn, Denise"],["dc.contributor.author","Liu, Shuxi"],["dc.contributor.author","Marco, Elysa J"],["dc.contributor.author","McDonald, Marie"],["dc.contributor.author","McWalter, Kirsty"],["dc.contributor.author","Race, Simone"],["dc.contributor.author","Rush, Eric T"],["dc.contributor.author","Si, Yue"],["dc.contributor.author","Saunders, Carol"],["dc.contributor.author","Slavotinek, Anne"],["dc.contributor.author","Stockler-Ipsiroglu, Sylvia"],["dc.contributor.author","Telegrafi, Aida"],["dc.contributor.author","Thiffault, Isabelle"],["dc.contributor.author","Torti, Erin"],["dc.contributor.author","Tsai, Anne Chun-Hui"],["dc.contributor.author","Wang, Xin"],["dc.contributor.author","Zafar, Muhammad"],["dc.contributor.author","Keren, Boris"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Boerkoel, Cornelius F"],["dc.contributor.author","Mirzaa, Ghayda"],["dc.contributor.author","Ehmke, Nadja"],["dc.date.accessioned","2020-06-23T10:09:44Z"],["dc.date.available","2020-06-23T10:09:44Z"],["dc.date.issued","2019"],["dc.description.abstract","Notch signaling is an established developmental pathway for brain morphogenesis. Given that Delta-like 1 (DLL1) is a ligand for the Notch receptor and that a few individuals with developmental delay, intellectual disability, and brain malformations have microdeletions encompassing DLL1, we hypothesized that insufficiency of DLL1 causes a human neurodevelopmental disorder. We performed exome sequencing in individuals with neurodevelopmental disorders. The cohort was identified using known Matchmaker Exchange nodes such as GeneMatcher. This method identified 15 individuals from 12 unrelated families with heterozygous pathogenic DLL1 variants (nonsense, missense, splice site, and one whole gene deletion). The most common features in our cohort were intellectual disability, autism spectrum disorder, seizures, variable brain malformations, muscular hypotonia, and scoliosis. We did not identify an obvious genotype-phenotype correlation. Analysis of one splice site variant showed an in-frame insertion of 12 bp. In conclusion, heterozygous DLL1 pathogenic variants cause a variable neurodevelopmental phenotype and multi-systemic features. The clinical and molecular data support haploinsufficiency as a mechanism for the pathogenesis of this DLL1-related disorder and affirm the importance of DLL1 in human brain development."],["dc.identifier.doi","10.1016/j.ajhg.2019.07.002"],["dc.identifier.pmid","31353024"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66647"],["dc.language.iso","en"],["dc.relation.eissn","1537-6605"],["dc.relation.issn","0002-9297"],["dc.title","Haploinsufficiency of the Notch Ligand DLL1 Causes Variable Neurodevelopmental Disorders"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]