Severe short stature and endogenous growth hormone resistance in twin brothers without growth hormone gene mutations

Emily C. Walvoord, Kyle W. Sloop, Conor J. Dwyer, Simon J. Rhodes, Ora H. Pescovitz

Research output: Contribution to journalArticle

Abstract

Growth failure in children with high growth hormone (GH) levels, low insulin-like growth factor 1 (IGF-1) levels, and accelerated linear growth in response to exogenous GH is presumed to result from biologically inactive GH. A molecular diagnosis has only been made in two such patients. We analyzed the presentations and the GH-1 genes of twin Egyptian brothers with this phenotype. At 8 yr of age, the boys' heights were -4 SD. Their IGF-1 levels were 64 and 60 ng/mL, baseline GH levels were 2.1 and 11.7 mU/L, and growth hormone binding protein levels were normal. Twin B attained a peak GH level of 30.6 mU/L after L-dopa stimulation (Twin A was not tested). After 1 yr of exogenous GH, their growth velocities were >11 cm/year (>97%). Analysis of their GH-1 exons and introns revealed no mutations, but five polymorphisms were identified that have not been previously reported. The GH-1 DNA sequence was transfected into human cells and the resulting GH-1 transcripts were analyzed. Wild-type GH-1 mRNAs were observed, demonstrating that the polymorphisms do not affect transcript processing. Therefore, although no evidence of GH-1 gene mutations or abnormal GH-1 mRNA processing was found, the subjects' excellent response to exogenous GH supports a trial of GH in children with severe short stature, low IGF-1 levels and normal GH responses to stimulation testing.

Original languageEnglish (US)
Pages (from-to)289-295
Number of pages7
JournalEndocrine
Volume21
Issue number3
DOIs
StatePublished - Aug 1 2003

Keywords

  • Biological activity
  • DNA analysis
  • Growth disorders
  • Somatotropin

ASJC Scopus subject areas

  • Endocrinology

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