title: Renal-coloboma syndrome: a single nucleotide deletion in the PAX2 gene at Exon 8 is associated with a highly variable phenotype.
abstract: BACKGROUND
  Renal-coloboma syndrome (RCS) is an autosomal dominant disorder characterized by renal abnormalities and optic nerve defects, caused by heterozygous mutations of the PAX2 gene. This gene encodes for the PAX2 developmental nuclear transcription factor, which is primarily expressed during embryogenesis in kidneys, eyes, ears and in the central nervous system. The aim of the present study was to characterize PAX2 mutations in a renal coloboma syndrome family with a highly variable phenotype.
  
  
  METHODS
  DNA screening was performed by direct sequencing.
  
  
  RESULTS
  Five subjects over three generations presented with renal hypodysplasia or horseshoe kidneys in association with bilateral optic nerve colobomas in four cases, one patient with early-onset renal failure had no detectable eye defects. All five subjects carried a novel PAX2 mutation consisting in a frameshift mutation located in Exon 8 (G91 I del), which causes premature termination of translation and loss of the PAX2 transactivation domain.
  
  
  CONCLUSIONS
  This is the first report of a PAX2 mutation located in Exon 8. The variability of clinical symptoms may be explained by the limited disruption of the protein sequence at the transactivation domain.
authors.affiliation: Department of Nephrology and Urology, Division of Nephrology, Bambino Gesu Children's Hospital, Piazza S. Onofrio, 4, 00165 Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Taranta
authors.forename: A
authors.initials: A
authors.lastname: Palma
authors.forename: V
authors.initials: V
authors.lastname: De Luca
authors.forename: A
authors.initials: A
authors.lastname: Romanzo
authors.forename: L
authors.initials: L
authors.lastname: Massella
authors.forename: F
authors.initials: F
authors.lastname: Emma
authors.forename: L
authors.initials: L
authors.lastname: Dello Strologo
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003103:Coloboma / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000002:abnormalities*; D009154:Mutation; D009900:Optic Nerve / Q000002:abnormalities*; D051762:PAX2 Transcription Factor / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human