title: SIX1 gene: absence of mutations in children with isolated congenital anomalies of kidney and urinary tract.
abstract: BACKGROUND
  Mutations in human SIX1 gene cause branchiootorenal or branchiootic syndrome. Six1 deficient mice exhibit uni- or bilateral renal hypoplasia or kidney agenesis. Furthermore a lack of Six1 gene in the ureter leads to hydroureter and hydronephrosis. These murine malformations resemble human kidney and urinary tract congenital anomalies (CAKUT), a group of diseases with a diverse anatomical spectrum which includes duplex collecting system as much as urethra kidney and ureteropelvic anomalies. Our study focuses on whether mutations or deletion of this gene may be associated with nonsyndromic CAKUT.
  
  
  METHODS
  Fifty unrelated patients (13-21 years) with nonsyndromic CAKUT were retrospectively recruited for SIX1 sequence variations analysis, and compared to three subjects without malformative nephrouropathies (controls). SIX1 coding sequence was screened by high resolution melt analysis (HRMA) and by Sanger direct sequencing. A quantitative comparative real-time polymerase chain reaction (PCR) was later performed in order to detect the presence of SIX1 gene deletion.
  
  
  RESULTS
  We did not find significant differences in the HRMA melting curves for each of the SIX1 coding exons between patients and controls, as also confirmed by Sanger direct sequencing. Moreover quantitative comparative real-time PCR for SIX1 and data normalization excluded total SIX1 gene deletion in our patients.
  
  
  CONCLUSIONS
  We did not find sequence variations in SIX1 coding regions or complete gene deletion in our CAKUT population. These results suggest that alterations in these sequences are unlikely to be a major cause of nonsyndromic CAKUT. Nevertheless, further studies are necessary to understand if altered SIX1 expression may play a role in human development of kidney and urinary tract congenital anomalies.
authors.affiliation: Laboratory of Immunopathology and Molecular Biology of the Kidney, Women's and Children's Health Department, University of Padua, Via Giustiniani 3, 35128, Padua, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Negrisolo
authors.affiliation: Laboratory of Immunopathology and Molecular Biology of the Kidney, Women's and Children's Health Department, University of Padua, Via Giustiniani 3, 35128, Padua, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Centi
authors.affiliation: Pediatric Nephrology, Dialysis and Transplant Unit, Women's and Children's Health Department, University of Padua, Via Giustiniani 3, 35128, Padua, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Benetti
authors.affiliation: Pediatric Nephrology, Dialysis and Transplant Unit, Women's and Children's Health Department, University of Padua, Via Giustiniani 3, 35128, Padua, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ghirardo
authors.affiliation: Laboratory of Immunopathology and Molecular Biology of the Kidney, Women's and Children's Health Department, University of Padua, Via Giustiniani 3, 35128, Padua, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Della Vella
authors.affiliation: Pediatric Nephrology, Dialysis and Transplant Unit, Women's and Children's Health Department, University of Padua, Via Giustiniani 3, 35128, Padua, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Murer
authors.affiliation: Laboratory of Immunopathology and Molecular Biology of the Kidney, Women's and Children's Health Department, University of Padua, Via Giustiniani 3, 35128, Padua, Italy. lina.artifoni@unipd.it.
authors.forename: Lina
authors.initials: L
authors.lastname: Artifoni
mesh_terms: D000293:Adolescent; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors; D014564:Urogenital Abnormalities / Q000175:diagnosis / Q000235:genetics*; D014718:Vesico-Ureteral Reflux / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C099236:SIX1 protein, human
keywords: CAKUT; Children; Kidney and urinary tract congenital anomalies; Renal transplant recipients; SIX1 gene