PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects

Nat Genet. 1994 Aug;7(4):463-71. doi: 10.1038/ng0894-463.


The human eye malformation aniridia results from haploinsufficiency of PAX6, a paired box DNA-binding protein. To study this dosage effect, we characterized two PAX6 mutations in a family segregating aniridia and a milder syndrome consisting of congenital cataracts and late onset corneal dystrophy. The nonsense mutations, at codons 103 and 353, truncate PAX6 within the N-terminal paired and C-terminal PST domains, respectively. The wild-type PST domain activates transcription autonomously and the mutant form has partial activity. A compound heterozygote had severe craniofacial and central nervous system defects and no eyes. The pattern of malformations is similar to that in homozygous Sey mice and suggests a critical role for PAX6 in controlling the migration and differentiation of specific neuronal progenitor cells in the brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Amino Acid Sequence
  • Animals
  • Aniridia / genetics
  • Anophthalmos / genetics
  • Base Sequence
  • Brain / abnormalities*
  • Cataract / congenital
  • Cataract / genetics
  • DNA / genetics
  • DNA Mutational Analysis
  • DNA Primers / genetics
  • DNA-Binding Proteins / genetics*
  • Eye Abnormalities / genetics*
  • Eye Proteins
  • Female
  • Homeodomain Proteins*
  • Homozygote
  • Humans
  • Infant, Newborn
  • Male
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pedigree
  • Point Mutation
  • Repressor Proteins


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