title: A novel homozygous HESX1 mutation causes panhypopituitarism without midline defects and optic nerve anomalies.
abstract: OBJECTIVE
  There are many genes reported to have been associated with combined pituitary hormone deficiencies, but mutations in HESX1 strongly correlate with septo-optic dysplasia. Our aim was to determine the cause of panhypopituitarism in our patient.
  
  
  METHODS
  We studied an 8-month-old child having panhypopituitarism. The coding exons of PIT1, PROP1, LHX3, and HESX1 genes were amplified. Direct sequencing was done after denaturing HLPC.
  
  
  RESULTS
  We identified a novel homozygous mutation (R160H) within the homeodomain of HESX1, which, to our knowledge, is the first to be described in humans. Neuroimaging studies revealed anterior pituitary aplasia, a normal posterior pituitary gland, and a thin pituitary stalk but no midline abnormalities. Optic nerve studies showed no pathology. This mutation is also carried in the parents of the affected child in a heterozygous pattern, suggesting an autosomal recessive inheritance.
  
  
  CONCLUSIONS
  These data demonstrate that homozygous HESX1 mutation causing an R160H substitution can result in panhypopituitarism without midline defects.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Ege University, Bornova, 35100 Izmir, Turkey. burak.durmaz@ege.edu.tr
authors.forename: Burak
authors.initials: B
authors.lastname: Durmaz
authors.forename: Ozgur
authors.initials: O
authors.lastname: Cogulu
authors.forename: Ceyhun
authors.initials: C
authors.lastname: Dizdarer
authors.forename: Heike
authors.initials: H
authors.lastname: Stobbe
authors.forename: Roland
authors.initials: R
authors.lastname: Pfaeffle
authors.forename: Ferda
authors.initials: F
authors.lastname: Ozkinay
mesh_terms: D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007018:Hypopituitarism / Q000235:genetics* / Q000473:pathology; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009900:Optic Nerve / Q000033:anatomy & histology*; D010902:Pituitary Gland / Q000002:abnormalities; D010903:Pituitary Gland, Anterior / Q000002:abnormalities; D010904:Pituitary Gland, Posterior / Q000033:anatomy & histology*; D017354:Point Mutation / Q000235:genetics; D025962:Septo-Optic Dysplasia / Q000235:genetics* / Q000473:pathology
chemical_list: C489736:HESX1 protein, human; D018398:Homeodomain Proteins