title: ROBO2 gene variants in children with primary nonsyndromic vesicoureteral reflux with or without renal hypoplasia/dysplasia.
abstract: Primary nonsyndromic vesicoureteral reflux (VUR) and VUR with renal hypoplasia/dysplasia (VUR-RHD) are common congenital anomalies of the kidney and urinary tract (CAKUT). Sequence variations of the ROBO2 gene were investigated in children with nonsyndromic VUR or VUR-RHD.
  
  
  
  Single-strand conformation polymorphism (SSCP) electrophoresis or multiple restriction fragment SSCP (MRF-SSCP), followed occasionally by direct sequencing, was used to screen 103 patients and 200 controls for nucleotide changes. Gene polymorphisms and transposable elements were investigated using bioinformatics.
  
  
  
  Two single-nucleotide polymorphisms were detected: IVS1-53 and IVS5-31. The frequency of A allele of IVS1-53G>A did not differ significantly between patients and controls. IVS1-53 does not affect mRNA splicing according to in silico analysis. IVS5-31A>G substitution was found in one patient, reported here for the first time in VUR. In silico results demonstrated alteration in two serine/arginine-rich (SR) protein-binding sites and two additional acceptor sites. The ROBO2 gene sequence was found to contain 25.9% transposable elements.
  
  
  
  ROBO2 variants were not found to be associated with nonsyndromic VUR or VUR-RHD, providing further evidence for genetic heterogeneity. The role of transposable elements in ROBO2 gene expression in CAKUT needs further investigation since they are generally considered to be mutagens.
authors.affiliation: Laboratory of Medical Genetics and Human Reproduction, School of Health Sciences, Faculty of Medicine University of Ioannina, Ioannina, Greece.
authors.forename: Artemis G
authors.initials: AG
authors.lastname: Mitsioni
authors.affiliation: Department of Pediatrics, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Siomou
authors.affiliation: Laboratory of Medical Genetics and Human Reproduction, School of Health Sciences, Faculty of Medicine University of Ioannina, Ioannina, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Bouba
authors.affiliation: Laboratory of Medical Genetics and Human Reproduction, School of Health Sciences, Faculty of Medicine University of Ioannina, Ioannina, Greece.
authors.forename: Stavroula
authors.initials: S
authors.lastname: Petridi
authors.affiliation: Department of Pediatrics, University Hospital of Ioannina, Ioannina, Greece.
authors.forename: Antigoni
authors.initials: A
authors.lastname: Siamopoulou
authors.affiliation: Laboratory of Medical Genetics and Human Reproduction, School of Health Sciences, Faculty of Medicine University of Ioannina, Ioannina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Georgiou
mesh_terms: D000483:Alleles; D001665:Binding Sites; D016022:Case-Control Studies; D002675:Child, Preschool; D019295:Computational Biology; D004251:DNA Transposable Elements; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000150:complications / Q000235:genetics*; D008297:Male; D009711:Nucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011971:Receptors, Immunologic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014718:Vesico-Ureteral Reflux / Q000150:complications / Q000235:genetics*; D000097905:Roundabout Proteins
chemical_list: D004251:DNA Transposable Elements; D009711:Nucleotides; D011971:Receptors, Immunologic; C498890:ROBO2 protein, human; D000097905:Roundabout Proteins