title: SOX3 deletion in mouse and human is associated with persistence of the craniopharyngeal canal.
abstract: BACKGROUND
  SOX3 is an early developmental transcription factor involved in pituitary development. In humans, over- and underdosage of SOX3 is associated with X-linked hypopituitarism with variable phenotypes ranging from isolated GH deficiency (GHD) to panhypopituitarism, with or without mental retardation and, in most cases, with reported pituitary imaging, an ectopic/undescended posterior pituitary.
  
  
  METHODS
  We present a young patient with hemophilia B and developmental delay who had a 2.31-Mb deletion on Xq27 including SOX3, F9, and eight other contiguous genes. He developed GH and gonadotropin deficiency, whilst his thyroid function was in the low normal range. Magnetic resonance imaging revealed a eutopic posterior pituitary and the unusual finding of a persistent craniopharyngeal canal that has not previously been described in patients with congenital hypopituitarism.
  
  
  OBJECTIVE
  To establish whether loss of SOX3 can account for the human phenotype, we examined in detail the hypothalamo-pituitary region of neonatal Sox3 null mice.
  
  
  RESULTS
  Consistent with the patient's phenotype, Sox3 null mice exhibit a ventral extension of the anterior pituitary that penetrates, and generates a mass beneath, the sphenoid bone. This suggests that the defect results from abnormal induction of Rathke's pouch, leading to a persistent connection between Rathke's pouch and the oral ectoderm.
  
  
  CONCLUSIONS
  Our observations expand the spectrum of phenotypes observed in association with altered SOX3 dosage and may affect the approach to genetic screening. Screening for SOX3 should be advised not only for hypopituitary patients with an ectopic posterior pituitary, but also for those with a structurally normal pituitary and additional findings, including clefts and a persistent craniopharyngeal canal, with or without mental retardation.
authors.affiliation: Developmental Endocrinology Research Group (K.S.A., M.T.D.), Clinical and Molecular Genetics Unit, University College London Institute of Child Health, London WC1N 1EH, United Kingdom; Department of Pediatric Endocrinology and Diabetes (A.A., F.R.), Oxford University Hospitals National Health Service (NHS) Trust, Oxford OX3 9DU, United Kingdom; School of Molecular and Biomedical Science (N.R., P.T.), The University of Adelaide, Adelaide SA 5005, Australia; Oxford Hemophilia and Thrombosis Centre (N.C., P.B.), and Departments of Clinical Genetics (C.N., H.S.) and Paediatric Hematology and Oncology (G.W.H.), Oxford University Hospitals NHS Trust, Oxford OX3 9DU, United Kingdom; Department of Radiology (A.S.L., D.S.), Great Ormond St Hospital for Children NHS Trust, London WC1N 1EH, United Kingdom.
authors.forename: K S
authors.initials: KS
authors.lastname: Alatzoglou
authors.forename: A
authors.initials: A
authors.lastname: Azriyanti
authors.forename: N
authors.initials: N
authors.lastname: Rogers
authors.forename: F
authors.initials: F
authors.lastname: Ryan
authors.forename: N
authors.initials: N
authors.lastname: Curry
authors.forename: C
authors.initials: C
authors.lastname: Noakes
authors.forename: P
authors.initials: P
authors.lastname: Bignell
authors.forename: G W
authors.initials: GW
authors.lastname: Hall
authors.forename: A S
authors.initials: AS
authors.lastname: Littooij
authors.forename: D
authors.initials: D
authors.lastname: Saunders
authors.forename: P
authors.initials: P
authors.lastname: Thomas
authors.forename: H
authors.initials: H
authors.lastname: Stewart
authors.forename: M T
authors.initials: MT
authors.lastname: Dattani
mesh_terms: D000818:Animals; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics; D017353:Gene Deletion; D002836:Hemophilia B / Q000235:genetics; D006801:Humans; D007018:Hypopituitarism / Q000235:genetics / Q000473:pathology; D007030:Hypothalamo-Hypophyseal System / Q000002:abnormalities / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000473:pathology; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D013100:Sphenoid Bone / Q000002:abnormalities* / Q000254:growth & development* / Q000473:pathology
chemical_list: C527785:SOX3 protein, human; D055748:SOXB1 Transcription Factors; C527786:Sox3 protein, mouse