• Open Access

SOX2 haploinsufficiency is associated with slow progressing hypothalamo-pituitary tumours

Authors

  • Kyriaki S. Alatzoglou,

    1. Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom
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    • These two authors contributed equally to this work.

  • Cynthia L. Andoniadou,

    1. Neural Development Unit, Institute of Child Health, University College London, London, United Kingdom
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    • These two authors contributed equally to this work.

  • Daniel Kelberman,

    1. Ulverscroft Vision Research Group, Developmental Biology Unit, Institute of Child Health, University College London, London, United Kingdom
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  • Charles R. Buchanan,

    1. Department of Child Health, Kings College Hospital NHS Foundation Trust, London, United Kingdom
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  • John Crolla,

    1. Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, United Kingdom
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  • Maria Cristina Arriazu,

    1. Department of Pediatric Endocrinology, Hospital Privado de Comunidad, Buenos Aires, Argentina
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  • Martin Roubicek,

    1. Department of Pediatric Endocrinology, Hospital Privado de Comunidad, Buenos Aires, Argentina
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  • Daniel Moncet,

    1. Department of Pediatric Endocrinology, Hospital Privado de Comunidad, Buenos Aires, Argentina
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  • Juan P. Martinez-Barbera,

    1. Neural Development Unit, Institute of Child Health, University College London, London, United Kingdom
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  • Mehul T. Dattani

    Corresponding author
    1. Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom
    • Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London WC1N, 1EH, United Kingdom.
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  • Communicated by Richard Wooster

Abstract

SOX2 is an early developmental transcription factor and marker of stem cells that has recently been implicated in the development of the pituitary gland. Heterozygous SOX2 mutations have been described in patients with hypopituitarism and severe ocular abnormalities. In the majority of published cases, the pituitary gland is either small or normal in size. Here, we report two unrelated patients with SOX2 haploinsufficiency (a heterozygous gene deletion and a novel c.143TC>AA/p.F48X mutation) who developed nonprogressive pituitary tumors of early onset, suggesting a congenital etiology. The truncating mutation resulted in significant loss of function and impaired nuclear localization of the mutant protein, in addition to a failure to repress β-catenin transcriptional activity in vitro. This is the first indication that SOX2 haploinsufficiency is implicated in the generation of pituitary tumors with distinct clinical characteristics, possibly mediated via its effects on the Wnt signaling pathway. 32:1376–1380, 2011. ©2011 Wiley Periodicals, Inc.

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