Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations

Am J Hum Genet. 1997 Apr;60(4):869-78.


Renal-coloboma syndrome is a recently described autosomal dominant syndrome of abnormal optic nerve and renal development. Two families have been reported with renal-coloboma syndrome and mutations of the PAX2 gene. The PAX2 gene, which encodes a DNA-binding protein, is expressed in the developing ear, CNS, eye, and urogenital tract. Ocular and/or renal abnormalities have been consistently noted in the five reports of patients with renal-coloboma syndrome, to date, but PAX2 expression patterns suggest that auditory and CNS abnormalities may be additional features of renal-coloboma syndrome. To determine whether additional clinical features are associated with PAX2 mutations, we have used PCR-SSCP to identify PAX2 gene mutations in patients. We report here four patients with mutations in exon 2, one of whom has severe ocular and renal disease, microcephaly, and retardation, and another who has ocular and renal disease with high-frequency hearing loss. Unexpectedly, extreme variability in clinical presentation was observed between a mother, her son, and an unrelated patient, all of whom had the same PAX2 mutation as previously described in two siblings with renal-coloboma syndrome. These results suggest that a sequence of seven Gs in PAX2 exon 2 may be particularly prone to mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adult
  • Child
  • Cloning, Molecular
  • Coloboma / genetics*
  • DNA-Binding Proteins / genetics*
  • Exons / genetics
  • Female
  • Genetic Variation
  • Humans
  • Kidney / abnormalities*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Optic Nerve / abnormalities*
  • PAX2 Transcription Factor
  • Phenotype
  • Sequence Analysis, DNA
  • Syndrome
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • PAX2 Transcription Factor
  • PAX2 protein, human
  • Transcription Factors

Associated data

  • GENBANK/Y07617