This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sjoberg, M. Articles by Mericq, M. V. Search for Related Content PubMed PubMed Citation Articles by Sjoberg, M. Articles by Mericq, M. V.

Study of GH Sensitivity in Chilean Patients with Idiopathic Short Stature

Institute of Maternal and Child Research (IDIMI) (T.S., A.A., M.E., F.C., M.V.M.) and Institute of Biomedical Sciences (M.S., C.E., A.D., P.C.), Faculty of Medicine, University of Chile; and Department of Cellular and Molecular Biology (M.S., C.E., P.C.), Faculty of Biological Sciences, Catholic University, Santiago, Chile

Address all correspondence and requests for reprints to: M. Verónica Mericq, IDIMI, University of Chile, Casilla 226–3, Santiago, Chile. E-mail: vmericq{at}machi.med.uchile.cl

Abstract

We hypothesized that some children with idiopathic short stature in Chile might bear heterozygous mutations of the GH receptor. We selected 26 patients (3 females, 23 males) from 112 patients who consulted for idiopathic short stature at the University of Chile. Their chronological age was 8.3 ± 1.9, and bone age was 6.1 ± 1.0 yr. Their height was -3.0 ± 0.7 SDS; IGF-I, -1.2 ± 1.1 SD; IGF binding protein 3, -0.7 ± 2.0 SDS; and GH binding protein, 0.4 ± 0.8 SDS. Patients were admitted, and blood samples were obtained every 20 min to determine GH concentrations overnight. Coding sequences and intron-exon boundaries of exons 2–10 of GH receptor gene were amplified by PCR and subsequently analyzed through single-strand conformational analysis. Mean serum GH concentration, over 12-h, was 0.20 ± 0.08 nM; pulse amplitude, 0.40 ± 0.15 nM; number of peaks, 5.8 ±1.5 peaks/12 h; peak value of GH during the 12-h sampling, 1.03 ± 0.53 nM; and area under the curve, 151.4 ± 56.1 nM/12 h. There were positive correlations between mean GH vs. area under the curve (P < 0.001) and GH peak (P < 0.01). The single-strand conformational analysis of the GH receptor gene showed abnormal migration for exon 6 in 9 patients and for exon 10 in 9 patients, which (by sequence analysis) corresponded to 2 polymorphisms of the GH receptor gene: an A-to-G transition in third position of codon 168 in exon 6 and a C-to-A transversion in the first position of codon 526 in exon 10. We further sequenced all coding exons and intron-exon boundaries in the most affected patients (nos. 6, 9, 11, 14, 15, 16, and 23). This analysis revealed a C-to-T transition in codon 161 of exon 6 in patient 23, which results in an amino acid change (Arg to Cys) in an heterozygous form in the patient and his father. In conclusion, the results of our study suggest that, in Chilean patients with idiopathic short stature, GH receptor gene mutations are uncommon, although we cannot exclude mutations that were missed by single-strand conformational analysis or mutations within introns or in the promoter regions of the GH receptor gene.

This article has been cited by other articles:

				A. Carrascosa, L. Audi, C. Esteban, M. Fernandez-Cancio, P. Andaluz, M. Gussinye, M. Clemente, D. Yeste, and M. A. Albisu Growth Hormone (GH) Dose, But Not Exon 3-Deleted/Full-Length GH Receptor Polymorphism Genotypes, Influences Growth Response to Two-Year GH Therapy in Short Small-for-Gestational-Age Children J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 147 - 153. [Abstract] [Full Text] [PDF]

				M. O Savage, C. Camacho-Hubner, A. David, L. A Metherell, V. Hwa, R. G Rosenfeld, and A. J L Clark Idiopathic short stature: will genetics influence the choice between GH and IGF-I therapy? Eur. J. Endocrinol., August 1, 2007; 157(suppl_1): S33 - S37. [Abstract] [Full Text] [PDF]

				A. Carrascosa, C. Esteban, R. Espadero, M. Fernandez-Cancio, P. Andaluz, M. Clemente, L. Audi, H. Wollmann, L. Fryklund, L. Parodi, et al. The d3/fl-Growth Hormone (GH) Receptor Polymorphism Does Not Influence the Effect of GH Treatment (66 {micro}g/kg per Day) or the Spontaneous Growth in Short Non-GH-Deficient Small-for-Gestational-Age Children: Results from a Two-Year Controlled Prospective Study in 170 Spanish Patients J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3281 - 3286. [Abstract] [Full Text] [PDF]

				A. Pilotta, P. Mella, M. Filisetti, B. Felappi, E. Prandi, G. Parrinello, L. D. Notarangelo, and F. Buzi Common Polymorphisms of the Growth Hormone (GH) Receptor Do Not Correlate with the Growth Response to Exogenous Recombinant Human GH in GH-Deficient Children J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1178 - 1180. [Abstract] [Full Text] [PDF]

				E. M. Dennison, H. E. Syddall, S. Rodriguez, A. Voropanov, I. N. M. Day, C. Cooper, and the Southampton Genetic Epidemiology Research Grou Polymorphism in the Growth Hormone Gene, Weight in Infancy, and Adult Bone Mass J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4898 - 4903. [Abstract] [Full Text] [PDF]