Genomic profiling in (recurrent) steroid-resistant nephrotic syndrome
Human Genetics
Final Report Abstract
Identification of the genetic basis of isolated or complex kidney diseases (diseases that not only affect the kidneys but also other organ systems) is already possible today for a substantial proportion of pediatric patients but for a relevant proportion of adult patients. New DNA sequencing methods such as the so-called long-read sequencing methods, which allow reading lengths of several tens of thousands of DNA bases in one piece, allow for a far better detection of structural DNA changes relevant to disease and thus further increase the rate of detectable genetic diseases. A definite molecular diagnosis can already contribute to better (symptomatic) treatment of kidney disease and is sometimes even capable of preventing the need for dialysis therapy for life. In addition, the identification of family members at risk and, if necessary, timely treatment of other family members using genetics is quick and efficient. This is particularly important in pediatric setting in of early-onset severe kidney dysfunction with the option of living donation by a parent, but also in many constellations in the field of adult nephrology. Not only can genomic methods be used to diagnose diseases, the release of cell-free DNA (cfDNA) into the bloodstream (and other body fluids such as urine) also allows the use of DNA as a biomarker for kidney diseases. In the future, patients who show a specific pattern of cell-free DNA released from their kidney tissue in the bloodstream that associates with a high risk of acute kidney injury could be continuously monitored and preemptively treated through a simple blood sample based cfDNA assay. Genetic finding that clarify the causes of mostly rare genetic kidney disease (rare) genetic kidney diseases will not only allow for targeted treatment of these diseases in the future, but can also be transferred to other, more common forms of chronic kidney diseases and can thus benefit a significantly larger group of patients.
Publications
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A molecular mechanism explaining albuminuria in kidney disease. Nature Metabolism, 2(5), 461-474.
Butt, Linus; Unnersjö-Jess, David; Höhne, Martin; Edwards, Aurelie; Binz-Lotter, Julia; Reilly, Dervla; Hahnfeldt, Robert; Ziegler, Vera; Fremter, Katharina; Rinschen, Markus M.; Helmstädter, Martin; Ebert, Lena K.; Castrop, Hayo; Hackl, Matthias J.; Walz, Gerd; Brinkkoetter, Paul T.; Liebau, Max C.; Tory, Kálmán; Hoyer, Peter F. ... & Benzing, Thomas
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cfNOMe —A single assay for comprehensive epigenetic analyses of cell-free DNA. Genome Medicine, 12(1).
Erger, Florian; Nörling, Deborah; Borchert, Domenica; Leenen, Esther; Habbig, Sandra; Wiesener, Michael S.; Bartram, Malte P.; Wenzel, Andrea; Becker, Christian; Toliat, Mohammad R.; Nürnberg, Peter; Beck, Bodo B. & Altmüller, Janine
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De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis. The American Journal of Human Genetics, 108(2), 357-367.
Weng, Patricia L.; Majmundar, Amar J.; Khan, Kamal; Lim, Tze Y.; Shril, Shirlee; Jin, Gina; Musgrove, John; Wang, Minxian; Ahram, Dina F.; Aggarwal, Vimla S.; Bier, Louise E.; Heinzen, Erin L.; Onuchic-Whitford, Ana C.; Mann, Nina; Buerger, Florian; Schneider, Ronen; Deutsch, Konstantin; Kitzler, Thomas M.; Klämbt, Verena ... & Sanna-Cherchi, Simone
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Expanding the Spectrum of FAT1 Nephropathies by Novel Mutations That Affect Hippo Signaling. Kidney International Reports, 6(5), 1368-1378.
Fabretti, Francesca; Tschernoster, Nikolai; Erger, Florian; Hedergott, Andrea; Buescher, Anja K.; Dafinger, Claudia; Reusch, Bjoern; Köntges, Vincent K.; Kohl, Stefan; Bartram, Malte P.; Weber, Lutz Thorsten; Thiele, Holger; Altmueller, Janine; Schermer, Bernhard; Beck, Bodo B. & Habbig, Sandra
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Alport syndrome and autosomal dominant tubulointerstitial kidney disease frequently underlie end-stage renal disease of unknown origin—a single-center analysis. Nephrology Dialysis Transplantation, 37(10), 1895-1905.
Leenen, Esther; Erger, Florian; Altmüller, Janine; Wenzel, Andrea; Thiele, Holger; Harth, Ana; Tschernoster, Nikolai; Lokhande, Shanti; Joerres, Achim; Becker, Jan-Ulrich; Ekici, Arif; Huettel, Bruno; Beck, Bodo & Weidemann, Alexander
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Lifelong effect of therapy in young patients with the COL4A5 Alport missense variant p.(Gly624Asp): a prospective cohort study. Nephrology Dialysis Transplantation, 37(12), 2496-2504.
Boeckhaus, Jan; Hoefele, Julia; Riedhammer, Korbinian M.; Nagel, Mato; Beck, Bodo B.; Choi, Mira; Gollasch, Maik; Bergmann, Carsten; Sonntag, Joseph E.; Troesch, Victoria; Stock, Johanna & Gross, Oliver
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Unraveling Structural Rearrangements of the CFH Gene Cluster in Atypical Hemolytic Uremic Syndrome Patients Using Molecular Combing and Long-Fragment Targeted Sequencing. The Journal of Molecular Diagnostics, 24(6), 619-631.
Tschernoster, Nikolai; Erger, Florian; Walsh, Patrick R.; McNicholas, Bairbre; Fistrek, Margareta; Habbig, Sandra; Schumacher, Anna-Lena; Folz-Donahue, Kat; Kukat, Christian; Toliat, Mohammad R.; Becker, Christian; Thiele, Holger; Kavanagh, David; Nürnberg, Peter; Beck, Bodo B. & Altmüller, Janine
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Germline C1GALT1C1 mutation causes a multisystem chaperonopathy. Proceedings of the National Academy of Sciences, 120(22).
Erger, Florian; Aryal, Rajindra P.; Reusch, Björn; Matsumoto, Yasuyuki; Meyer, Robert; Zeng, Junwei; Knopp, Cordula; Noel, Maxence; Muerner, Lukas; Wenzel, Andrea; Kohl, Stefan; Tschernoster, Nikolai; Rappl, Gunter; Rouvet, Isabelle; Schröder-Braunstein, Jutta; Seibert, Felix S.; Thiele, Holger; Häusler, Martin G.; Weber, Lutz T. ... & Beck, Bodo B.
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Long-read sequencing identifies a common transposition haplotype predisposing for CLCNKB deletions. Genome Medicine, 15(1).
Tschernoster, Nikolai; Erger, Florian; Kohl, Stefan; Reusch, Björn; Wenzel, Andrea; Walsh, Stephen; Thiele, Holger; Becker, Christian; Franitza, Marek; Bartram, Malte P.; Kömhoff, Martin; Schumacher, Lena; Kukat, Christian; Borodina, Tatiana; Quedenau, Claudia; Nürnberg, Peter; Rinschen, Markus M.; Driller, Jan H.; Pedersen, Bjørn P. ... & Altmüller, Janine
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Modeling of ACTN4-Based Podocytopathy Using Drosophila Nephrocytes. Kidney International Reports, 8(2), 317-329.
Odenthal, Johanna; Dittrich, Sebastian; Ludwig, Vivian; Merz, Tim; Reitmeier, Katrin; Reusch, Björn; Höhne, Martin; Cosgun, Zülfü C.; Hohenadel, Maximilian; Putnik, Jovana; Göbel, Heike; Rinschen, Markus M.; Altmüller, Janine; Koehler, Sybille; Schermer, Bernhard; Benzing, Thomas; Beck, Bodo B.; Brinkkötter, Paul T.; Habbig, Sandra & Bartram, Malte P.
