A novel exonic GHR splicing mutation (c.784G>C) in a patient with classical growth hormone insensitivity syndrome

Ayşehan Aknc, Ron G. Rosenfeld, Vivian Hwa

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Context: Undetectable circulating growth hormone-binding protein (GHBP) can be indicative of a GH receptor (GHR) defect and cause GH insensitivity (GHI) syndrome. Case Report: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)32-38
Number of pages7
JournalHormone Research in Paediatrics
Issue number1
StatePublished - 2013
Externally publishedYes


  • Exon-intron junctions
  • GHR splicing
  • Growth hormone insensitivity
  • Insulin-like growth factor-I therapy
  • c.784G>C mutation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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