Kolvenbach, Caroline M., Dworschak, Gabriel C., Frese, Sandra, Japp, Anna S., Schuster, Peggy, Wenzlitschke, Nina, Yilmaz, Oeznur, Lopes, Filipa M., Pryalukhin, Alexey, Schierbaum, Luca, van der Zanden, Loes F. M., Kause, Franziska, Schneider, Ronen, Taranta-Janusz, Katarzyna ORCID: 0000-0002-8762-8866, Szczepanska, Maria ORCID: 0000-0002-6772-1983, Pawlaczyk, Krzysztof, Newman, William G., Beaman, Glenda M., Stuart, Helen M., Cervellione, Raimondo M., Feitz, Wouter F. J., van Rooij, Iris A. L. M., Schreuder, Michiel F., Steffens, Martijn, Weber, Stefanie, Merz, Waltraut M., Feldkoetter, Markus, Hoppe, Bernd, Thiele, Holger, Altmueller, Janine, Berg, Christoph, Kristiansen, Glen, Ludwig, Michael, Reutter, Heiko, Woolf, Adrian S., Hildebrandt, Friedhelm, Grote, Phillip, Zaniew, Marcin, Odermatt, Benjamin and Hilger, Alina C. (2019). Rare Variants in BNC2 Are Implicated in Autosomal-Dominant Congenital Lower Urinary-Tract Obstruction. Am. J. Hum. Genet., 104 (5). S. 994 - 1007. CAMBRIDGE: CELL PRESS. ISSN 1537-6605

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Abstract

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. Resequencing 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kolvenbach, Caroline M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dworschak, Gabriel C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frese, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Japp, Anna S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuster, PeggyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wenzlitschke, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yilmaz, OeznurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopes, Filipa M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pryalukhin, AlexeyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schierbaum, LucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Zanden, Loes F. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kause, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, RonenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taranta-Janusz, KatarzynaUNSPECIFIEDorcid.org/0000-0002-8762-8866UNSPECIFIED
Szczepanska, MariaUNSPECIFIEDorcid.org/0000-0002-6772-1983UNSPECIFIED
Pawlaczyk, KrzysztofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Newman, William G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beaman, Glenda M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stuart, Helen M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cervellione, Raimondo M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feitz, Wouter F. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Rooij, Iris A. L. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreuder, Michiel F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steffens, MartijnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merz, Waltraut M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feldkoetter, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoppe, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berg, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kristiansen, GlenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ludwig, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reutter, HeikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woolf, Adrian S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hildebrandt, FriedhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grote, PhillipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zaniew, MarcinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odermatt, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hilger, Alina C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-148633
DOI: 10.1016/j.ajhg.2019.03.023
Journal or Publication Title: Am. J. Hum. Genet.
Volume: 104
Number: 5
Page Range: S. 994 - 1007
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1537-6605
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
POSTERIOR URETHRAL VALVES; MOLECULAR-BASIS; BASONUCLIN 2; MUTATIONS; PENETRANCE; MANAGEMENT; DIAGNOSISMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14863

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