PUBLICATION
Rare Variants in BNC2 Are Implicated in Autosomal-Dominant Congenital Lower Urinary-Tract Obstruction
- Authors
- Kolvenbach, C.M., Dworschak, G.C., Frese, S., Japp, A.S., Schuster, P., Wenzlitschke, N., Yilmaz, Ö., Lopes, F.M., Pryalukhin, A., Schierbaum, L., van der Zanden, L.F.M., Kause, F., Schneider, R., Taranta-Janusz, K., Szczepańska, M., Pawlaczyk, K., Newman, W.G., Beaman, G.M., Stuart, H.M., Cervellione, R.M., Feitz, W.F.J., van Rooij, I.A.L.M., Schreuder, M.F., Steffens, M., Weber, S., Merz, W.M., Feldkötter, M., Hoppe, B., Thiele, H., Altmüller, J., Berg, C., Kristiansen, G., Ludwig, M., Reutter, H., Woolf, A.S., Hildebrandt, F., Grote, P., Zaniew, M., Odermatt, B., Hilger, A.C.
- ID
- ZDB-PUB-190507-29
- Date
- 2019
- Source
- American journal of human genetics 104: 994-1006 (Journal)
- Registered Authors
- Hildebrandt, Friedhelm, Odermatt, Benjamin, Schneider, Ronen
- Keywords
- BNC2, LUTO, basonuclin 2, cloacae, distal pronephric outlet obstruction, functional genetics, lower urinary tract obstruction, posterior urethral valve, pronephric development, zebrafish
- MeSH Terms
-
- Adult
- Animals
- Child
- Chromosome Aberrations*
- DNA-Binding Proteins/genetics*
- Female
- Fetal Diseases/genetics*
- Fetal Diseases/pathology
- Genes, Dominant
- Gestational Age
- Humans
- Male
- Mice
- Middle Aged
- Mutation*
- Pedigree
- Pregnancy
- Urinary Bladder Neck Obstruction/congenital*
- Urinary Bladder Neck Obstruction/genetics*
- Urinary Bladder Neck Obstruction/pathology
- Zebrafish
- PubMed
- 31051115 Full text @ Am. J. Hum. Genet.
Citation
Kolvenbach, C.M., Dworschak, G.C., Frese, S., Japp, A.S., Schuster, P., Wenzlitschke, N., Yilmaz, Ö., Lopes, F.M., Pryalukhin, A., Schierbaum, L., van der Zanden, L.F.M., Kause, F., Schneider, R., Taranta-Janusz, K., Szczepańska, M., Pawlaczyk, K., Newman, W.G., Beaman, G.M., Stuart, H.M., Cervellione, R.M., Feitz, W.F.J., van Rooij, I.A.L.M., Schreuder, M.F., Steffens, M., Weber, S., Merz, W.M., Feldkötter, M., Hoppe, B., Thiele, H., Altmüller, J., Berg, C., Kristiansen, G., Ludwig, M., Reutter, H., Woolf, A.S., Hildebrandt, F., Grote, P., Zaniew, M., Odermatt, B., Hilger, A.C. (2019) Rare Variants in BNC2 Are Implicated in Autosomal-Dominant Congenital Lower Urinary-Tract Obstruction. American journal of human genetics. 104:994-1006.
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. 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping