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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 454456 (2007) | Download Citation

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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.

Author information

Author notes

    • Sylvain Briault

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

Affiliations

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

    • Lekbir Baala
    • , Abdelhafid Natiq
    • , Aziza Sbiti
    •  & Abdelaziz Sefiani
  2. INSERM U781, Hôpital Necker, Département de Génétique, 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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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Stanislas Lyonnet.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Clinical features.

  2. 2.

    Supplementary Fig. 2

    FISH analyses of BACs RP11-9A14 (chromosome 3p) and RP11-102H24 (chromosome 10q).

  3. 3.

    Supplementary Fig. 3

    Sequencing of the junction fragments on 3p24 and 10q22.

  4. 4.

    Supplementary Table 1

    BAC probes encompassing the 3p and 10q translocation breakpoint.

  5. 5.

    Supplementary Table 2

    Methods for RT-PCR analysis of candidate genes on chromosome 3p and 10q.

  6. 6.

    Supplementary Methods

  7. 7.

    Supplementary Note

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DOI

https://doi.org/10.1038/ng1993

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