Address of Corresponding Author

Horm Res 2006;65:210-216 (DOI: 10.1159/000092514)

  Key Words

• Growth hormone receptor
• Idiopathic short stature
• Growth hormone insensitivity
• Growth hormone binding protein
• Insulin-like growth factor I, binding protein 3
• Growth hormone deficiency

  Abstract

Background/Aims: In children with short stature, in whom growth hormone deficiency has been excluded, the presence of a normal or elevated growth hormone concentration concomitant with low insulin-like growth factor I suggests growth hormone insensitivity (GHI). Previous reports suggest that heterozygous mutations in the growth hormone receptor gene (GHR) may account for about 5% of children with idiopathic short stature (ISS). In the present study we have attempted to determine whether mutations in the GHR explain the short stature and growth retardation in a cohort of children with ISS and characteristics suggesting GHI. Methods: For the present study 33 children with clinical and biochemical characteristics of GHI were selected from a cohort of 150 children of short stature. Molecular analysis of the GHR was performed using a single-strand conformation polymorphism technique and sequencing. Ten different sequence changes in 19 (58%) out of 33 children were identified, 9 of them novel and 1 that had been described previously. Results: Two changes were found in exons 2 and 6. The known polymorphism of exon 6 (G168) was significantly more common in the control subjects than in our study group (63.5 vs. 30%; p < 0.0001). In the intronic sequences 8 previously undescribed DNA changes were found. The screening of the affected children's family members revealed that both normal and short stature members carried the same variants. The study group did not significantly differ from the controls in retention (GHRfl) or exclusion (GHRd3) of exon 3. Conclusion: Our study suggests that sequence changes of the GHR are common in children with ISS. The presence of these sequence changes in the control subjects as well as in normal stature family members indicates that these changes represent a simple polymorphism of the GHR. Such DNA changes are more prevalent than previously recognized, and they do not seem to play a contributory role in the etiology of short stature.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Dr. Yardena Tenenbaum-Rakover
Head of the Pediatric Endocrine Unit
Ha' Emek Medical Center
Afula, 18101 (Israel)
Tel. +972 4649 5203, Fax +972 4649 5289, E-Mail rakover_y@clalit.org.il

  Article Information

Received: August 12, 2005
Accepted: February 20, 2006
Published online: March 31, 2006
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 3, Number of References : 26