Gross, Oliver

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Pediatric Nephrology"],["dc.bibliographiccitation.lastpage","10"],["dc.contributor.author","Rheault, Michelle N."],["dc.contributor.author","Savige, Judith"],["dc.contributor.author","Randles, Michael J."],["dc.contributor.author","Weinstock, André"],["dc.contributor.author","Stepney, Melissa"],["dc.contributor.author","Turner, A Neil"],["dc.contributor.author","Parziale, Gina"],["dc.contributor.author","Gross, Oliver"],["dc.contributor.author","Flinter, Frances A"],["dc.contributor.author","Miner, Jeffrey H"],["dc.contributor.author","Lagas, Sharon"],["dc.contributor.author","Gear, Susie"],["dc.contributor.author","Lennon, Rachel"],["dc.date.accessioned","2019-07-09T11:51:36Z"],["dc.date.available","2019-07-09T11:51:36Z"],["dc.date.issued","2019"],["dc.description.abstract","Alport syndrome is caused by mutations in the genes COL4A3, COL4A4 or COL4A5 and is characterised by progressive glomerular disease, sensorineural hearing loss and ocular defects. Occurring in less than 1:5000, Alport syndrome is a rare genetic disorder but still accounts for > 1% of the prevalent population receiving renal replacement therapy. There is also increasing awareness about the risk of chronic kidney disease in individuals with heterozygous mutations in Alport syndrome genes. The mainstay of current therapy is the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, yet potential new therapies are now entering clinical trials. The 2017 International Workshop on Alport Syndrome in Glasgow was a pre-conference workshop ahead of the 50th anniversary meeting of the European Society for Pediatric Nephrology. It focussed on updates in clinical practice, genetics and basic science and also incorporated patient perspectives. More than 80 international experts including clinicians, geneticists, researchers from academia and industry, and patient representatives took part in panel discussions and breakout groups. This report summarises the workshop proceedings and the relevant contemporary literature. It highlights the unique clinician, patient and researcher collaborations achieved by regular engagement between the groups."],["dc.identifier.doi","10.1007/s00467-019-04241-7"],["dc.identifier.pmid","31044288"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16151"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59970"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1432-198X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","The importance of clinician, patient and researcher collaborations in Alport syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Fibrogenesis & Tissue Repair"],["dc.bibliographiccitation.lastpage","10"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Girgert, Rainer"],["dc.contributor.author","Martin, Maria"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Miosge, Nicolai"],["dc.contributor.author","Temme, Johanna"],["dc.contributor.author","Eckes, Beate"],["dc.contributor.author","Müller, Gerhard-Anton"],["dc.contributor.author","Gross, Oliver"],["dc.date.accessioned","2019-07-09T11:52:48Z"],["dc.date.available","2019-07-09T11:52:48Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Integrins are important cellular receptors for collagens. Within the glomerulus, podocytes regulate the integrity of the glomerular basement membrane (GBM) by sensing the presence of collagen and regulating collagen IV synthesis. The present study evaluates the role of integrin a2 (ITGA2) in cell-matrix interaction. Methods and Results: ITGA2-deficient mice had normal renal function but moderate proteinuria and enhanced glomerular and tubulointerstitial matrix deposition. Electron microscopy demonstrated irregular podocyte-matrix interaction, causing pathological protrusions towards the urinary (podocyte) side of the GBM. These characteristic subepithelial bulges mimic the renal phenotype of mice, which are deficient in another collagen receptor, discoidin domain receptor (DDR)1. Using immunogold staining, ITGA2 expression was found to localize to the basolateral site of the podocyte foot processes. ITGA2-deficient mice overexpressed transforming growth factor (TGF)b and connective tissue growth factor (CTGF) compared with wild-type mice. Using in situ hybridization, tubular cells were found to be the primary site of TGFb synthesis and podocytes the source of CTGF in ITGA2- deficient mice. Conclusion: These findings support our hypothesis that both these collagen receptors (ITGA2 and DDR1) play a similar role within the kidney. Further, cell-matrix interaction via collagen receptors seems to be crucial for maintenance of normal GBM architecture and function. Targeting collagen receptors such as ITGA2 might be a new form of treatment for progressive fibrotic diseases."],["dc.identifier.doi","10.1186/1755-1536-3-19"],["dc.identifier.fs","575629"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6018"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60281"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/6905 but duplicate"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Integrin a2-deficient mice provide insights into specific functions of collagen receptors in the kidney"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","429"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Medizinische Genetik"],["dc.bibliographiccitation.lastpage","437"],["dc.contributor.author","Gross, Oliver"],["dc.contributor.author","Hoefele, Julia"],["dc.date.accessioned","2019-07-09T11:50:42Z"],["dc.date.available","2019-07-09T11:50:42Z"],["dc.date.issued","2019"],["dc.description.abstract","Patients with the hereditary disease Alport syndrome (AS) develop progressive renal fibrosis due to variants in type IV collagen genes. In the first years of life, AS starts with hematuria and proteinuria, finally leading to end-stage renal disease and extrarenal symptoms such as hearing impairment and ocular changes. Variants in three different genes can cause AS, COL4A5 (X-chromosomal) in 85%, COL4A3 or COL4A4 (autosomal) in 10%, and digenic variants in less than 5% of the cases. In the past, the symptomatic form in patients with a heterozygous variant was classified as thin basement membrane disease or benign familial hematuria. However, patients with a heterozygous variant often have a non-benign disease course. Therefore, these patients are now also given the diagnosis “Alport syndrome.” If diagnosed early, AS is treatable. Renal failure can be delayed by years and life expectancy can be improved. Because of the available treatment options, the molecular genetic diagnosis should be made as soon as possible in every affected child and in all patients with a heterozygous variant. Unfortunately, the diagnosis is often made too late during early adolescence. This article serves as a guideline for the genetic background of AS, possible additional (genetic) modifiers, possible additional complications, and the current therapeutic approach for the optimal lifelong care of patients living with AS. For genetic experts, it is important to know that this nephroprotective approach begins with an early genetic diagnosis guiding the timeline of possible therapeutic interventions."],["dc.description.abstract","Bei der Typ IV Kollagen-Erkrankung Alport-Syndrom (AS) handelt es sich um eine progressive hereditäre Nephropathie. Klinische Zeichen sind zunächst Hämaturie und Proteinurie, im weiteren Verlauf kommt es zu einem terminalen Nierenversagen. Zusätzlich werden extrarenale Manifestationen wie Innenohr-Schwerhörigkeit und Augenveränderungen beobachtet. Man unterscheidet drei Erbgänge: 85 % der Fälle sind X-chromosomal, ca. 10 % autosomal und weniger als 5 % digenisch. Ursächlich sind Varianten in den Kollagen Typ IV-Genen COL4A3, COL4A4 (beide autosomal) und COL4A5 (X-chromosomal). Die Symptomatik heterozygoter Anlageträger wurde früher als benigne familiäre Hämaturie bezeichnet. Da Anlageträger jedoch häufig keinen benignen Verlauf zeigen, werden sie inzwischen auch unter der Diagnose „Alport-Syndrom“ geführt. Der Humangenetiker hat daher beim AS eine wichtige Lotsenfunktion: Bei früher Diagnose ist das AS inzwischen gut behandelbar, wodurch das terminale Nierenversagen um mehrere Jahre hinausgezögert und damit die Lebenserwartung verbessert werden kann. Aufgrund der Therapiemöglichkeiten sollte die (molekulargenetische) Diagnose bei Betroffenen, auch bei heterozygoten Anlageträgern, frühzeitig gestellt werden. Mit diesem Artikel sollen die genetischen Ursachen des AS, mögliche genetische Einflussfaktoren auf den variablen Phänotyp, die unterschiedlichen Krankheitsstadien, Komplikationen sowie die derzeit zugelassene Behandlung aufgezeigt werden, um eine bestmögliche lebenslange Betreuung des Patienten zu gewährleisten."],["dc.identifier.doi","10.1007/s11825-018-0214-2"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15981"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59812"],["dc.language.iso","de"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1863-5490"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Genetische Ursachen und Therapie beim Alport-Syndrom"],["dc.title.translated","Genetic causes and therapy in Alport Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","519"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","20"],["dc.contributor.affiliation","Frese, Jenny; \t\t \r\n\t\t Clinic of Nephrology and Rheumatology, University Medical Center Goettingen, 37075 Goettingen, Germany, jenny.frese@dpdhl.com"],["dc.contributor.affiliation","Kettwig, Matthias; \t\t \r\n\t\t Clinic of Pediatrics and Adolescent Medicine, University Medical Center Goettingen, 37075 Goettingen, Germany, matthias.kettwig@med.uni-goettingen.de"],["dc.contributor.affiliation","Zappel, Hildegard; \t\t \r\n\t\t Clinic of Pediatrics and Adolescent Medicine, University Medical Center Goettingen, 37075 Goettingen, Germany, hzappel@med.uni-goettingen.de"],["dc.contributor.affiliation","Hofer, Johannes; \t\t \r\n\t\t Department of Pediatrics, Pediatrics I, Innsbruck Medical University, 6020 Innsbruck, Austria, Johannes.Hofer@i-med.ac.at"],["dc.contributor.affiliation","Gröne, Hermann-Josef; \t\t \r\n\t\t Department of Cellular and Molecular Pathology, German Cancer Research Center, 69120 Heidelberg, Germany, h.-j.groene@dkfz-heidelberg.de"],["dc.contributor.affiliation","Nagel, Mato; \t\t \r\n\t\t Center for Nephrology and Metabolic Disorders, Molecular Diagnostics, 02943 Weißwasser, Germany, nagel@moldiag.de"],["dc.contributor.affiliation","Sunder-Plassmann, Gere; \t\t \r\n\t\t Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria, Gere.Sunder-Plassmann@meduniwien.ac.at"],["dc.contributor.affiliation","Kain, Renate; \t\t \r\n\t\t Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria, renate.kain@meduniwien.ac.at"],["dc.contributor.affiliation","Neuweiler, Jörg; \t\t \r\n\t\t Institute of Pathology, Kantonsspital, 9007 St. Gallen, Switzerland, joerg.neuweiler@kssg.ch"],["dc.contributor.affiliation","Gross, Oliver; \t\t \r\n\t\t Clinic of Nephrology and Rheumatology, University Medical Center Goettingen, 37075 Goettingen, Germany, gross.oliver@med.uni-goettingen.de"],["dc.contributor.author","Frese, Jenny"],["dc.contributor.author","Kettwig, Matthias"],["dc.contributor.author","Zappel, Hildegard"],["dc.contributor.author","Hofer, Johannes"],["dc.contributor.author","Gröne, Hermann-Josef"],["dc.contributor.author","Nagel, Mato"],["dc.contributor.author","Sunder-Plassmann, Gere"],["dc.contributor.author","Kain, Renate"],["dc.contributor.author","Neuweiler, Jörg"],["dc.contributor.author","Gross, Oliver"],["dc.date.accessioned","2019-07-09T11:50:02Z"],["dc.date.available","2019-07-09T11:50:02Z"],["dc.date.issued","2019"],["dc.date.updated","2022-09-05T07:17:34Z"],["dc.description.abstract","Kidney injury due to focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder causing end-stage renal disease. Homozygous mutations in either glomerular basement membrane or slit diaphragm genes cause early renal failure. Heterozygous carriers develop renal symptoms late, if at all. In contrast to mutations in slit diaphragm genes, hetero- or hemizygous mutations in the X-chromosomal COL4A5 Alport gene have not yet been recognized as a major cause of kidney injury by FSGS. We identified cases of FSGS that were unexpectedly diagnosed: In addition to mutations in the X-chromosomal COL4A5 type IV collagen gene, nephrin and podocin polymorphisms aggravated kidney damage, leading to FSGS with ruptures of the basement membrane in a toddler and early renal failure in heterozygous girls. The results of our case series study suggest a synergistic role for genes encoding basement membrane and slit diaphragm proteins as a cause of kidney injury due to FSGS. Our results demonstrate that the molecular genetics of different players in the glomerular filtration barrier can be used to evaluate causes of kidney injury. Given the high frequency of X-chromosomal carriers of Alport genes, the analysis of genes involved in the organization of podocyte architecture, the glomerular basement membrane, and the slit diaphragm will further improve our understanding of the pathogenesis of FSGS and guide prognosis of and therapy for hereditary glomerular kidney diseases."],["dc.identifier.doi","10.3390/ijms20030519"],["dc.identifier.pmid","30691124"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15841"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59686"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1422-0067"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Kidney Injury by Variants in the COL4A5 Gene Aggravated by Polymorphisms in Slit Diaphragm Genes Causes Focal Segmental Glomerulosclerosis."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]