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

Nature Genetics volume 39, pages 454–456 (2007)Cite this article

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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Figure 1: Segregation, genetic and fine physical mapping of the disease locus.
Figure 2: Silencing of the translocated EOMES locus and normal EOMES expression in the developing human brain.

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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.

Author information

Author notes

  1. Sylvain Briault

    Present address: Present address: Laboratoire de génétique, CHR La Source, Orléans, France.,

Authors and Affiliations

  1. Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Maroc

    Lekbir Baala, Abdelhafid Natiq, Aziza Sbiti & Abdelaziz Sefiani

  2. Département de Génétique, INSERM U781, Hôpital Necker, Paris, France

    Lekbir Baala, Heather C Etchevers, Jeanne Amiel, Tania Attié-Bitach, Féréchté Encha-Razavi, Arnold Munnich & Stanislas Lyonnet

  3. INSERM U619, Faculté de Médecine, Tours, France

    Sylvain Briault & Frédéric Laumonnier

  4. Hôpital Necker, Service de Radiologie Pédiatrique, Paris, France

    Nathalie Boddaert

  5. Centre d'étude des déficits immunitaires, Paris, France

    Capucine Picard

  6. Hôpital d'Enfants CHU Avicenne, Rabat, Maroc

    Abdellah Asermouh

  7. Université Réné Descartes - Paris 5, Paris, France

    Tania Attié-Bitach, Féréchté Encha-Razavi, Arnold Munnich & Stanislas Lyonnet

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  1. Lekbir Baala
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  15. Stanislas Lyonnet
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Corresponding author

Correspondence to Stanislas Lyonnet.

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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)

Supplementary Methods (PDF 123 kb)

Supplementary Note (PDF 79 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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