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SOX2 haploinsufficiency is associated with slow progressing hypothalamo-pituitary tumours.

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 ?-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.

SUBMITTER: Alatzoglou KS

PROVIDER: S-EPMC3487182 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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SOX2 haploinsufficiency is associated with slow progressing hypothalamo-pituitary tumours.

Alatzoglou Kyriaki S KS Andoniadou Cynthia L CL Kelberman Daniel D Buchanan Charles R CR Crolla John J Arriazu Maria Cristina MC Roubicek Martin M Moncet Daniel D Martinez-Barbera Juan P JP Dattani Mehul T MT

Human mutation 20111011 12

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 ...[more]

PMID: 21919124

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SOX2 haploinsufficiency is associated with slow progressing hypothalamo-pituitary tumours.

Publications

SOX2 haploinsufficiency is associated with slow progressing hypothalamo-pituitary tumours.

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