Heterozygous PAX6 mutation, adult brain structure and fronto-striato-thalamic function in a human family

Eur J Neurosci. 2004 Mar;19(6):1505-12. doi: 10.1111/j.1460-9568.2004.03236.x.


Recent progress in developmental neurobiology and neuroimaging can be drawn together to provide new insight into the links between genetically specified processes of embryonic brain development and adult human brain structure and function. We used magnetic resonance imaging (MRI) to show that individuals with aniridia and deficits in executive and social cognition, due to heterozygous mutation of the neurodevelopmental control gene PAX6, have structural abnormalities of grey matter in anterior cingulate cortex, cerebellum and medial temporal lobe, as well as white matter deficits in corpus callosum. Functional MRI demonstrated reduced activation of fronto-striato-thalamic systems during performance of overt verbal fluency and nonsense sentence completion; the most consistent abnormality of verbal executive activation was located in the thalamus. These results provide the first evidence for brain functional differences in humans with PAX6 mutation that are compatible both with anatomical abnormalities in the same subjects and, more circumstantially, with the known roles of murine Pax6 in regional differentiation, axonal guidance and other aspects of early forebrain development. Highly conserved homeobox genes may be critical for normal ontogenesis of large-scale neurocognitive networks supporting phylogenetically advanced mental functions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aniridia / complications
  • Aniridia / genetics
  • Brain / anatomy & histology
  • Brain / physiology*
  • Brain Mapping
  • Case-Control Studies
  • Cognition Disorders / etiology
  • Cognition Disorders / genetics
  • Eye Proteins
  • Family Health*
  • Female
  • Heterozygote*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Mutation*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Repressor Proteins
  • Social Conditions
  • Verbal Behavior / physiology


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