title: No TAP63 promoter mutation is detected in bladder exstrophy-epispadias complex patients.
abstract: OBJECTIVE
  Bladder exstrophy-epispadias complex (BEEC) is thought to have a genetic component in its pathogenesis. Previously we found that p63(-/-) mice show increased ventral apoptosis and develop a BEEC phenotype. Down-regulation of the anti-apoptotic ΔNP63 and an up-regulation of pro-apoptotic TAP63 isoforms have been demonstrated in BEEC patient bladder tissues. We have previously shown that insertion/deletion polymorphisms of the ΔNp63 promoter are associated with an increased risk of BEEC. In this study, we specifically examined the TAP63 promoter to see if any sequence changes might lead to up-regulation of TAP63 and exaggerated apoptosis in BEEC patients.
  
  
  METHODS
  i) Bioinformatic analysis of the TAP63 promoter was performed to identify putative regulatory regions. ii) High-resolution Melt and Sanger sequencing was used to screen targeted regions in 112 BEEC patient DNA samples for potential sequence variants. iii) Sequence variation was analysed for significance against normal population frequency data.
  
  
  RESULTS
  i) We identified multiple epigenetic markers of transcriptional regulation within highly conserved areas of the TAP63 promoter sequence. ii) Of the 112 buccal swab DNA samples, adequate and successful screening ranged between 48 and 67 for each region. iii) No novel sequence variation or mutation was uncovered. iv) Two known SNPs were identified. However, allele frequency analysis was not statistically significant.
  
  
  CONCLUSIONS
  Our data do not associate genetic variation within the TAP63 promoter region with an increased risk of BEEC. Our data so far suggests that only ΔNP63 promoter aberration is involved in BEEC pathogenesis.
authors: Monash Institute of Medical Research, Monash University, Melbourne, Australia.
authors: Tom
authors: T
authors: Darling
authors: Istiak
authors: I
authors: Mahfuz
authors: Stefan J
authors: SJ
authors: White
authors: Wei
authors: W
authors: Cheng
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D001746:Bladder Exstrophy / Q000235:genetics*; D015331:Cohort Studies; D019295:Computational Biology; D004842:Epispadias / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D005819:Genetic Markers; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: BEEC; Bladder exstrophy; TAP63; p63