Atypical GH insensitivity syndrome and severe insulin-like growth factor-I deficiency resulting from compound heterozygous mutations of the GH receptor, including a novel frameshift mutation affecting the intracellular domain

Javier Aisenberg, Valerie Auyeung, Helio F. Pedro, Rachel Sugalski, Amy Chartoff, Rachel Rothenberg, Michael A. Derr, Vivian Hwa, Ronald (Ron) Rosenfeld

Research output: Contribution to journalArticle

12 Scopus citations


Background/Aims: GH insensitivity and IGF deficiency may result from aberrations of the GH receptor (GHR). We describe a 4-year-old child with modest growth failure and normal serum concentrations of GH-binding protein (GHBP), but clinical evidence of GH insensitivity. Method: Serum and DNA samples from the proband and his parents were analyzed. Results: The child had a height of -4 SD, elevated serum GH concentrations, abnormally low serum IGF-I and IGFBP-3 concentrations and normal GHBP concentrations. DNA analysis revealed compound heterozygosity for mutations of GHR, including a previously reported R211H mutation and a novel duplication of a nucleotide in exon 9 (899dupC), the latter resulting in a frameshift and a premature stop codon. Treatment with recombinant DNA-derived IGF-I resulted in growth acceleration. Conclusion: Mutations affecting the intracellular domain of the GHR can result in GH insensitivity and IGF deficiency, despite normal serum concentrations of GHBP. The presence of clinical and biochemical evidence of GH resistance is sufficient to consider the possibility of aberrations of the GHR, even in the presence of normal serum GHBP concentrations.

Original languageEnglish (US)
Pages (from-to)406-411
Number of pages6
JournalHormone Research in Paediatrics
Issue number6
Publication statusPublished - Dec 2010



  • Atypical GH insensitivity
  • GH receptor defect
  • Short stature

ASJC Scopus subject areas

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

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