Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations

Am J Hum Genet. 2003 Jun;72(6):1565-70. doi: 10.1086/375555. Epub 2003 Apr 29.


The PAX6 gene is involved in ocular morphogenesis and is expressed in the developing central nervous system and numerous ocular tissues during development. PAX6 mutations have been detected in various ocular anomalies, including aniridia, Peters anomaly, corneal dystrophy, congenital cataracts, and foveal hypoplasia. However, it has not been identified in patients with optic-nerve malformations. Here, we identified novel mutations in eight pedigrees with optic-nerve malformations, including coloboma, morning glory disc anomaly, optic-nerve hypoplasia/aplasia, and persistent hyperplastic primary vitreous. A functional assay demonstrated that each mutation decreased the transcriptional activation potential of PAX6 through the paired DNA-binding domain. PAX6 and PAX2 are each thought to downregulate the expression of the other. Four of the detected mutations affected PAX6-mediated transcriptional repression of the PAX2 promoter in a reporter assay. Because PAX2 gene mutations were detected in papillorenal syndrome, alternation of PAX2 function by PAX6 mutations may affect phenotypic manifestations of optic-nerve malformations.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Base Sequence
  • Cell Line
  • Child, Preschool
  • Eye Proteins
  • Female
  • Genes, Suppressor
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Optic Nerve / abnormalities*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pedigree
  • Promoter Regions, Genetic
  • Repressor Proteins
  • Transcriptional Activation


  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Repressor Proteins

Associated data

  • GENBANK/M93650
  • GENBANK/U45245
  • GENBANK/U63833