title: A novel exonic GHR splicing mutation (c.784G > C) in a patient with classical growth hormone insensitivity syndrome.
abstract: BACKGROUND
  Undetectable circulating growth hormone-binding protein (GHBP) can be indicative of a GH receptor (GHR) defect and cause GH insensitivity (GHI) syndrome.
  
  
  METHODS
  The proband, severely growth retarded from birth, had a height of 73 cm (-6 SDS) and weight of 10.5 kg (-2.5 SDS) at the age of 3.25 years; her consanguineous parents were normal statured. Basal serum GH measurement was high, >40 ng/ml, while serum insulin-like growth factor-I (IGF-I; 8.5 ng/ml; normal, 13-100), IGF-binding protein 3 (126 ng/ml; normal, 365-1,294), acid labile subunit (0.59 mg/l; normal, 5.6-16), and GHBP (120 pmol/l; normal, 431-1,892) concentrations were all markedly low. Recombinant IGF-I therapy improved height to -4.4 SDS after 2.5 years of treatment.
  
  
  RESULTS
  GHR gene analysis revealed a homozygous c.784G>C transversion, the last nucleotide of exon 7; the parents were heterozygous for the mutation. Evaluation of GHR mRNA indicated c.784G>C was not a missense mutation but induced exon 7 excision, leading to a frame shift and predicted early protein termination.
  
  
  CONCLUSIONS
  A novel homozygous GHRc.784G>C mutation, identified in a GHI patient, induced functional loss of the native intron 7 donor splice site, demonstrating, for the first time, the importance of exonic nucleotides at exon-intron junctions for normal GHR splicing.
authors.affiliation: Department of Pediatric Endocrinology, Turgut Özal Medical Center, İnonu University, Malatya, Turkey. aysehan.akinci@inonu.edu.tr
authors.forename: Ayşehan
authors.initials: A
authors.lastname: Akıncı
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld
authors.forename: Vivian
authors.initials: V
authors.lastname: Hwa
mesh_terms: D005091:Exons / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000627:therapeutic use; D007438:Introns / Q000235:genetics; D046150:Laron Syndrome / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011986:Receptors, Somatotropin / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I