Psychiatric disorder and cognitive function in a family with an inherited novel mutation of the developmental control gene PAX6

Psychiatr Genet. 1999 Jun;9(2):85-90. doi: 10.1097/00041444-199906000-00006.

Abstract

The PAX family of developmental control genes are known to play important roles in the early patterning of the central nervous system. One member of this family, PAX6, is involved in eye development in invertebrates as well as in mouse and man, but is also widely expressed in the developing forebrain. Humans with a mutation in this gene have abnormalities of eye development, and the results presented here suggest, for the first time, that this mutation may also be associated with subtle abnormalities of frontal lobe function in the family studied. We carried out genotyping of individuals within a single family, with and without the characteristic eye abnormalities of PAX6 mutation, and only those individuals with the mutation showed significant abnormalities on tests of frontal lobe function. These individuals also had higher rates of psychiatric disorder. PAX6 is highly conserved between mouse and man, and although the neuroanatomical phenotype associated with PAX6 heterozygosity has only been studied in mice, the resultant cellular disorganization seen in mice is likely to be present in the human forebrain. Although these mice have no obvious behavioural phenotype, the results presented here suggest that humans with the equivalent mutation display a neurobehavioural phenotype.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Aniridia / genetics*
  • Base Sequence
  • Body Patterning
  • Child
  • Chromosome Mapping
  • Cognition Disorders / genetics*
  • Cognition*
  • DNA-Binding Proteins / genetics*
  • Exons
  • Eye Proteins / genetics
  • Female
  • Heterozygote
  • Homeodomain Proteins*
  • Humans
  • Introns
  • Lod Score
  • Male
  • Mental Disorders / genetics*
  • Mice
  • Mutation*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Repressor Proteins

Substances

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