論文 - 詳細
| RRC ID | 76508 |
|---|---|
| 著者 | Kolvenbach CM, Dworschak GC, Frese S, Japp AS, Schuster P, Wenzlitschke N, Yilmaz Ö, Lopes FM, Pryalukhin A, Schierbaum L, van der Zanden LFM, Kause F, Schneider R, Taranta-Janusz K, Szczepańska M, Pawlaczyk K, Newman WG, Beaman GM, Stuart HM, Cervellione RM, Feitz WFJ, van Rooij IALM, Schreuder MF, Steffens M, Weber S, Merz WM, Feldkötter M, Hoppe B, Thiele H, Altmüller J, Berg C, Kristiansen G, Ludwig M, Reutter H, Woolf AS, Hildebrandt F, Grote P, Zaniew M, Odermatt B, Hilger AC. |
| タイトル | Rare Variants in BNC2 Are Implicated in Autosomal-Dominant Congenital Lower Urinary-Tract Obstruction. |
| ジャーナル | Am J Hum Genet |
| 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. |
| 巻・号 | 104(5) |
| ページ | 994-1006 |
| 公開日 | 2019-5-2 |
| DOI | 10.1016/j.ajhg.2019.03.023 |
| PII | S0002-9297(19)30119-3 |
| PMID | 31051115 |
| PMC | PMC6506863 |
| MeSH | 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 |
| IF | 10.502 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 12 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | HGj4A |