SOX2 haploinsufficiency is associated with slow progressing hypothalamo-pituitary tumours

Kyriaki S Alatzoglou, Cynthia L Andoniadou, Daniel Kelberman, Charles Buchanan, John Crolla, Maria Cristina Arriazu, Martin Roubicek, Daniel Moncet, Juan P Martinez-Barbera, Mehul T Dattani

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1376-1380
Number of pages5
JournalRegular Referee -Human Mutation
Issue number12
Publication statusPublished - Dec 2011


  • Adolescent
  • Female
  • Gene Deletion
  • HEK293 Cells
  • Haploinsufficiency
  • Heterozygote
  • Humans
  • Hypopituitarism
  • Hypothalamic Neoplasms
  • Infant
  • Male
  • Mutation
  • Pituitary Gland
  • SOXB1 Transcription Factors
  • Wnt Signaling Pathway
  • beta Catenin


Dive into the research topics of 'SOX2 haploinsufficiency is associated with slow progressing hypothalamo-pituitary tumours'. Together they form a unique fingerprint.

Cite this