title: Hypogonadotropic hypogonadism in an adult female with a heterozygous hypomorphic mutation of SOX2.
abstract: OBJECTIVE
  Heterozygous SOX2 mutations have recently been reported to cause isolated hypogonadotropic hypogonadism (HH), in addition to ocular and brain abnormalities. Here, we report a further case with a heterozygous hypomorphic SOX2 mutation and isolated HH.
  
  
  METHODS
  The patient was a 28-year-old Japanese female with congenital right anophthalmia and poor pubertal development, who was found to have HH by a gonadotropin-releasing hormone test (peak serum LH, 2.3 mIU/ml; peak serum FSH, 2.9 mIU/ml). Other pituitary hormones were normal.
  
  
  METHODS
  We performed mutation analysis of SOX2 and functional studies of mutant SOX2 protein using the core enhancer sequence of the chicken delta-1-crystallin gene (DC5) and that of the mouse nestin gene (Nes30).
  
  
  RESULTS
  A heterozygous missense mutation (224T > A, Leu75Gln) was identified in the DNA-binding domain. The mutant SOX2 protein had a severely reduced (approximately 10%) DNA-binding affinity and a markedly diminished (20-30%) transactivation potential with no dominant negative effect.
  
  
  CONCLUSIONS
  The results provide further support for the positive role of SOX2 in the regulation of gonadotropin production.
authors.affiliation: Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sato
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kamachi
authors.forename: Hisato
authors.initials: H
authors.lastname: Kondoh
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shima
authors.forename: Ken-ichirou
authors.initials: K
authors.lastname: Morohashi
authors.forename: Reiko
authors.initials: R
authors.lastname: Horikawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000328:Adult; D000853:Anophthalmos / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D024002:HMGB Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D020125:Mutation, Missense; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D024002:HMGB Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors