Abstract
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.
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Acknowledgements
The authors thank the microcephaly syndrome family for their participation. We thank Z. Al-Houssaini, N. Bahi-Buisson, C. Chirol, M. Clément-Ziza, N. Moussok, A. Pelet, S. Romana, C. Schatz and M. Vekemans for their assistance. This study was funded by INSERM, Agence Nationale de la Recherche and the Fondation pour le Recherche Médicale.
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Supplementary information
Supplementary Fig. 1
Clinical features. (PDF 387 kb)
Supplementary Fig. 2
FISH analyses of BACs RP11-9A14 (chromosome 3p) and RP11-102H24 (chromosome 10q). (PDF 139 kb)
Supplementary Fig. 3
Sequencing of the junction fragments on 3p24 and 10q22. (PDF 426 kb)
Supplementary Table 1
BAC probes encompassing the 3p and 10q translocation breakpoint. (PDF 65 kb)
Supplementary Table 2
Methods for RT-PCR analysis of candidate genes on chromosome 3p and 10q. (PDF 108 kb)
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Baala, L., Briault, S., Etchevers, H. et al. Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis. Nat Genet 39, 454–456 (2007). https://doi.org/10.1038/ng1993
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DOI: https://doi.org/10.1038/ng1993
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