title: Screening of LHX2 in patients presenting growth retardation with posterior pituitary and ocular abnormalities.
abstract: BACKGROUND
  In humans, pituitary hormone deficiency may be part of a syndrome including extra-pituitary defects like ocular abnormalities. Very few genes have been linked to this particular phenotype. In the mouse, Lhx2, which encodes a member of the LIM (Lin-11, Isl-1, and Mec-3) class of homeodomain proteins, was shown to be expressed during early development in the posterior pituitary, eye, and liver, and its expression persists in adulthood in the central nervous system Lhx2(-/-) mice display absence of posterior pituitary and intermediate lobes, malformation of the anterior lobe, anophthalmia, and they die from anemia.
  
  
  METHODS
  We tested the implication of the LHX2 gene in patients presenting pituitary hormone deficiency associated with ectopic or nonvisible posterior pituitary and developmental ocular defects. A cohort of 59 patients, including two familial cases, was studied. Direct sequencing of the LHX2 coding sequence and intron/exon boundaries was performed. LHX2 transcriptional activity on several pituitary promoters (AGSU, PRL, POU1F1, and TSHB) was tested in vitro.
  
  
  RESULTS
  Six heterozygous sequence variations were identified, among which two are novel missense changes (p.Ala203Thr and p.Val333Met). In vitro, LHX2 activates transcription of TSHB, PRL, and POU1F1 promoters in the HEK293 cell line. A synergistic action of POU1F1 and LHX2 was also shown on these promoters. The two missense variations were tested and no significant difference was observed, leading to the conclusion that they are not deleterious.
  
  
  CONCLUSIONS
  These results suggest that if LHX2 is involved in pituitary hormone deficiency associated with posterior pituitary and ocular defects, it would be a rare cause of this disease condition.
authors.affiliation: Inserm U.933, Hôpital Armand-Trousseau, Université Pierre et Marie Curie-Paris 6, 75571 Paris Cedex 12, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Pérez
authors.forename: Florence
authors.initials: F
authors.lastname: Dastot-Le Moal
authors.forename: Nathalie
authors.initials: N
authors.lastname: Collot
authors.forename: Marie
authors.initials: M
authors.lastname: Legendre
authors.forename: Isabelle
authors.initials: I
authors.lastname: Abadie
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bertrand
authors.forename: Serge
authors.initials: S
authors.lastname: Amselem
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Sobrier
mesh_terms: D000328:Adult; D001766:Blindness / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005820:Genetic Testing; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007223:Infant; D060850:LIM-Homeodomain Proteins / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D009900:Optic Nerve / Q000002:abnormalities; D009901:Optic Nerve Diseases / Q000235:genetics*; D010904:Pituitary Gland, Posterior / Q000002:abnormalities*; D011401:Promoter Regions, Genetic; D025962:Septo-Optic Dysplasia / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C489783:LHX2 protein, human; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors