title: Allelic variations in the human growth hormone-1 gene promoter of growth hormone-deficient patients and normal controls.
abstract: OBJECTIVE
  Isolated growth hormone deficiency (IGHD) type IB is suggested to be more probably due to alterations in the genes directly involved in the hypothalamo-pituitary axis and/or in the specific transcriptional regulation (cis-trans coupling) of the hGH-1 gene than to alterations in the gene itself. In this study we analyzed the hGH-1 gene promoter region for structural alterations and allelic variations.
  
  
  METHODS
  The hGH-1 gene promoter region was analyzed by PCR, cycle sequencing and direct-blotting electrophoresis in a total of 212 individuals including 113 patients with IGHD type IB, 21 unaffected family members and 78 normal controls.
  
  
  RESULTS
  Twenty-two sequence variation sites were identified. Of these, 14% were located around the region of -1075bp, 77% between -550bp and the translational start site (+1bp) and 9% within the first intron. Only one variation site affected a characterized cis-acting element, namely that of NF-1. Importantly, all the variations found in patients were also observed in non-affected family members as well as in normal unrelated controls.
  
  
  CONCLUSIONS
  These findings imply that it is not a single variation within the GH-1 gene promoter, and therefore in the cis-acting elements, which causes IGHD. However, we can not exclude the possibility that combinations of variations might perturb expression. Furthermore, these data illustrate the normal heterogeneity of the GH-1 gene promoter region, a fact that has to be borne in mind whenever transcriptional studies are performed.
authors.affiliation: Department of Pediatrics, University of Bern, Switzerland.
authors.forename: J K
authors.initials: JK
authors.lastname: Wagner
authors.forename: A
authors.initials: A
authors.lastname: Eblé
authors.forename: J D
authors.initials: JD
authors.lastname: Cogan
authors.forename: M A
authors.initials: MA
authors.lastname: Prince
authors.forename: J A
authors.initials: JA
authors.lastname: Phillips
authors.forename: P E
authors.initials: PE
authors.lastname: Mullis
mesh_terms: D000483:Alleles; D001483:Base Sequence; D014644:Genetic Variation / Q000235:genetics*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010375:Pedigree; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012016:Reference Values
chemical_list: D019382:Human Growth Hormone