Quantitative MR image analysis in subjects with defects in the PAX6 gene

Neuroimage. 2003 Dec;20(4):2281-90. doi: 10.1016/j.neuroimage.2003.07.001.

Abstract

Cerebral development is governed by genetic and environmental factors. Animal models provide much of our knowledge about genetic influences in the brain but it is not clear how similar or relevant these are to the human brain. The investigation of human subjects with mutations in genes known to be expressed in the developing brain is an alternative approach to improving our understanding of the role of genetic factors in brain development. We investigated 24 subjects with known mutations in the PAX6 gene (including representatives of all the known mutations of the gene) which are associated with characteristic ocular abnormalities in humans and animals. We have quantified MRI data using several techniques to assess qualities of cerebral structure which are difficult to interpret visually. Abnormalities were identified using voxel-based morphometry, statistical morphometrics, and measurement of corpus callosum cross-sectional area when comparing data from subjects with PAX6 abnormality and 72 age-and sex-matched control subjects. These abnormalities include grey matter changes in the cerebellum and occipital poles and white matter loss in the corpus callosum, alteration of sulcal orientation in the occipital lobe, and alteration to overall neuronal connectivity. These abnormalities complement and exceed the changes seen in the mouse models, and those seen on visual inspection alone of the human MRI data. Structural differences were also identified between the two largest genotype mutation subgroups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Aniridia / genetics
  • Aniridia / pathology
  • Brain / pathology*
  • Corpus Callosum / pathology
  • Eye Proteins
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Mutation / physiology*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Repressor Proteins

Substances

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