title: Genetics of human congenital urinary bladder disease.
abstract: Lower urinary tract and/or kidney malformations are collectively the most common cause of end-stage renal disease in children, and they are also likely to account for a major subset of young adults requiring renal replacement therapy. Advances have been made regarding the discovery of the genetic causes of human kidney malformations. Indeed, testing for mutations of key nephrogenesis genes is now feasible for patients seen in nephrology clinics. Unfortunately, less is known about defined genetic bases of human lower urinary tract anomalies. The focus of this review is the genetic bases of congenital structural and functional disorders of the urinary bladder. Three are highlighted. First, prune belly syndrome, where mutations of CHRM3, encoding an acetylcholine receptor, HNF1B, encoding a transcription factor, and ACTA2, encoding a cytoskeletal protein, have been reported. Second, the urofacial syndrome, where mutations of LRIG2 and HPSE2, encoding proteins localised in nerves invading the fetal bladder, have been defined. Finally, we review emerging evidence that bladder exstrophy may have genetic bases, including variants in the TP63 promoter. These genetic discoveries provide a new perspective on a group of otherwise poorly understood diseases.
authors.affiliation: Centre for Paediatrics Child Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK, adrian.woolf@manchester.ac.uk.
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Woolf
authors.forename: Helen M
authors.initials: HM
authors.lastname: Stuart
authors.forename: William G
authors.initials: WG
authors.lastname: Newman
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D001746:Bladder Exstrophy / Q000235:genetics; D004195:Disease Models, Animal; D019066:Facies; D020022:Genetic Predisposition to Disease; D005966:Glucuronidase / Q000235:genetics; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D009154:Mutation; D010641:Phenotype; D011535:Prune Belly Syndrome / Q000235:genetics; D043587:Receptor, Muscarinic M3 / Q000235:genetics; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D001743:Urinary Bladder / Q000002:abnormalities* / Q000503:physiopathology; D001745:Urinary Bladder Diseases / Q000151:congenital / Q000235:genetics* / Q000503:physiopathology; D014570:Urologic Diseases / Q000235:genetics; D000099175:Heparanase
chemical_list: D000199:Actins; D005966:Glucuronidase; D051539:Hepatocyte Nuclear Factor 1-beta; D008562:Membrane Glycoproteins; D043587:Receptor, Muscarinic M3; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000099175:Heparanase; C541116:ACTA2 protein, human; C496495:HNF1B protein, human; C488673:LRIG2 protein, human; C115051:TP63 protein, human