Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis

Nat Genet. 2007 Apr;39(4):454-6. doi: 10.1038/ng1993. Epub 2007 Mar 11.


Neural progenitor proliferation and migration influence brain size during neurogenesis. We report an autosomal recessive microcephaly syndrome cosegregating with a homozygous balanced translocation between chromosomes 3p and 10q, and we show that a position effect at the breakpoint on chromosome 3 silences the eomesodermin transcript (EOMES), also known as T-box-brain2 (TBR2). Together with the expression pattern of EOMES in the developing human brain, our data suggest that EOMES is involved in neuronal division and/or migration. Thus, mutations in genes encoding not only mitotic and apoptotic proteins but also transcription factors may be responsible for malformative microcephaly syndromes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology
  • Agenesis of Corpus Callosum*
  • Chromosomes, Human, Pair 10
  • Chromosomes, Human, Pair 3
  • DNA Mutational Analysis
  • Gene Silencing*
  • Homozygote*
  • Humans
  • Male
  • Microcephaly / genetics*
  • Pedigree
  • T-Box Domain Proteins / genetics*
  • Translocation, Genetic


  • EOMES protein, human
  • T-Box Domain Proteins