Caroline Kolvenbach, Gabriel Clemens Dworschak, Sandra Frese, Anna Sophia Japp, Peggy Schuster, Nina Wenzlitschke, Öznur Yilmaz, Filipa M. Lopes, Alexey Pryalukhin, Luca Schierbaum, Loes F. M. van der Zanden, Franziska Kause, Ronen Schneider, Katarzyna Taranta-Janusz, Maria Szczepańska, Krzysztof Pawlaczyk, William G. Newman, Glenda M. Beaman, Helen Stuart, Raimondo M. Cervellione, Wouter F. J. Feitz, Iris Antonia Leonarda Martina van Rooij, Michiel F. Schreuder, Martijn Steffens, Stefanie Weber, Waltraut Maria Merz, Markus Feldkötter, Bernd Hoppe, Holger Thiele, Janine Altmüller, Christoph Berg, Glen Kristiansen, Michael Ludwig, Heiko Reutter, Adrian S. Woolf, Friedhelm Hildebrandt, Phillip Grote, Marcin Zaniew, Benjamin Odermatt, Alina Christine Hilger
- Congenital lower urinary-tract obstruction (LUTO) is caused by anatomical blockage of the bladder outflow tract or by functional impairment of urinary voiding. About three out of 10,000 pregnancies are affected. Although several monogenic causes of functional obstruction have been defined, it is unknown whether congenital LUTO caused by anatomical blockage has a monogenic cause. Exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853∗]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage.
MetadatenAuthor: | Caroline KolvenbachORCiDGND, Gabriel Clemens DworschakGND, Sandra Frese, Anna Sophia Japp, Peggy Schuster, Nina Wenzlitschke, Öznur Yilmaz, Filipa M. Lopes, Alexey Pryalukhin, Luca Schierbaum, Loes F. M. van der Zanden, Franziska Kause, Ronen Schneider, Katarzyna Taranta-Janusz, Maria Szczepańska, Krzysztof Pawlaczyk, William G. NewmanORCiD, Glenda M. Beaman, Helen Stuart, Raimondo M. Cervellione, Wouter F. J. Feitz, Iris Antonia Leonarda Martina van RooijORCiDGND, Michiel F. Schreuder, Martijn Steffens, Stefanie Weber, Waltraut Maria Merz, Markus Feldkötter, Bernd Hoppe, Holger ThieleORCiD, Janine AltmüllerORCiDGND, Christoph Berg, Glen Kristiansen, Michael Ludwig, Heiko ReutterORCiDGND, Adrian S. WoolfORCiD, Friedhelm HildebrandtORCiDGND, Phillip GroteORCiD, Marcin Zaniew, Benjamin Odermatt, Alina Christine HilgerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-502648 |
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DOI: | https://doi.org/10.1016/j.ajhg.2019.03.023 |
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ISSN: | 1537-6605 |
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ISSN: | 0002-9297 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31051115 |
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Parent Title (English): | The American journal of human genetics |
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Publisher: | Cell Press ; Elsevier |
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Place of publication: | New York, NY [u. a.] |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2019 |
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Date of first Publication: | 2019/05/02 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2019/05/20 |
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Tag: | BNC2; LUT; Oposterior urethral valve; basonuclin 2; cloacae; distal pronephric outlet obstruction; functional genetics; lower urinary tract obstruction; pronephric development; zebrafish |
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Volume: | 104 |
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Issue: | 5 |
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Page Number: | 13 |
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First Page: | 994 |
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Last Page: | 1006 |
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Note: | © 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
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HeBIS-PPN: | 451035739 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |
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