title: Mutational analyses of UPIIIA, SHH, EFNB2 and HNF1beta in persistent cloaca and associated kidney malformations.
abstract: OBJECTIVE
  'Persistent cloaca' is a severe malformation affecting females in which the urinary, genital and alimentary tracts share a single conduit. Previously, a Uroplakin IIIA (UPIIIA) mutation was reported in one individual with persistent cloaca, and UPIIIA, Sonic Hedgehog (SHH), Ephrin B2 (EFNB2) and Hepatocyte Nuclear Factor 1beta (HNF1beta) are expressed during the normal development of organs that are affected in this condition. HNF1beta mutations have been associated with uterine malformations in humans, and mutations of genes homologous to human SHH or EFNB2 cause persistent cloaca in mice.
  
  
  METHODS
  We sought mutations of coding regions of UPIIIA, SHH, EFNB2 and HNF1beta genes by direct sequencing in a group of 20 patients with persistent cloaca. Most had associated malformations of the upper renal tract and over half had impaired renal excretory function. The majority of patients had congenital anomalies outside the renal/genital tracts and two had the VACTERL association.
  
  
  RESULTS
  Apart from a previously described index case, we failed to find UPIIIA mutations, and no patient had a SHH, EFNB2 or HNF1beta mutation.
  
  
  CONCLUSIONS
  Persistent cloaca is only rarely associated with UPIIIA mutation. Despite the fact that SHH and EFNB2 are appealing candidate genes, based on their expression patterns and mutant mice phenotypes, they were not mutated in these humans with persistent cloaca. Although HNF1beta mutations can perturb paramesonephric duct fusion in humans, HNF1beta was not mutated in persistent cloaca.
authors.affiliation: Nephro-Urology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WCIN IEH, UK.
authors.forename: Dagan
authors.initials: D
authors.lastname: Jenkins
authors.forename: Maria
authors.initials: M
authors.lastname: Bitner-Glindzicz
authors.forename: Louise
authors.initials: L
authors.lastname: Thomasson
authors.forename: Sue
authors.initials: S
authors.lastname: Malcolm
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Warne
authors.forename: Sally A
authors.initials: SA
authors.lastname: Feather
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Coralie
authors.initials: C
authors.lastname: Bingham
authors.forename: Lane
authors.initials: L
authors.lastname: Santos
authors.forename: Mark
authors.initials: M
authors.lastname: Henkemeyer
authors.forename: Andrew
authors.initials: A
authors.lastname: Zinn
authors.forename: Linda A
authors.initials: LA
authors.lastname: Baker
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Wilcox
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Woolf