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

Thomas M Glaser, L. Jepeal, J. G. Edwards, S. R. Young, J. Favor, R. L. Maas

Research output: Contribution to journalArticle

562 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)463-471
Number of pages9
JournalNature Genetics
Volume7
Issue number4
DOIs
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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