TY  - JOUR
A1  - Kolvenbach, Caroline
A1  - Dworschak, Gabriel Clemens
A1  - Frese, Sandra
A1  - Japp, Anna Sophia
A1  - Schuster, Peggy
A1  - Wenzlitschke, Nina
A1  - Yilmaz, Öznur
A1  - Lopes, Filipa M.
A1  - Pryalukhin, Alexey
A1  - Schierbaum, Luca
A1  - Zanden, Loes F. M. van der
A1  - Kause, Franziska
A1  - Schneider, Ronen
A1  - Taranta-Janusz, Katarzyna
A1  - Szczepańska, Maria
A1  - Pawlaczyk, Krzysztof
A1  - Newman, William G.
A1  - Beaman, Glenda M.
A1  - Stuart, Helen
A1  - Cervellione, Raimondo M.
A1  - Feitz, Wouter F. J.
A1  - Rooij, Iris Antonia Leonarda Martina van
A1  - Schreuder, Michiel F.
A1  - Steffens, Martijn
A1  - Weber, Stefanie
A1  - Merz, Waltraut Maria
A1  - Feldkötter, Markus
A1  - Hoppe, Bernd
A1  - Thiele, Holger
A1  - Altmüller, Janine
A1  - Berg, Christoph
A1  - Kristiansen, Glen
A1  - Ludwig, Michael
A1  - Reutter, Heiko
A1  - Woolf, Adrian S.
A1  - Hildebrandt, Friedhelm
A1  - Grote, Phillip
A1  - Zaniew, Marcin
A1  - Odermatt, Benjamin
A1  - Hilger, Alina Christine
T1  - Rare variants in BNC2 are implicated in autosomal-dominant congenital lower urinary-tract obstruction
T2  - The American journal of human genetics
N2  - 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.
KW  - lower urinary tract obstruction
KW  - LUT
KW  - Oposterior urethral valve
KW  - basonuclin 2
KW  - BNC2
KW  - zebrafish
KW  - functional genetics
KW  - pronephric development
KW  - cloacae
KW  - distal pronephric outlet obstruction
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50264
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-502648
SN  - 1537-6605
SN  - 0002-9297
N1  - © 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/).
VL  - 104
IS  - 5
SP  - 994
EP  - 1006
PB  - Cell Press ; Elsevier
CY  - New York, NY [u. a.]
ER  -