Growth Hormone Receptor Gene (GHR) Heterozygous Variants in Idiopathic

M.G. BALLERINI; P. SCAGLIA; A. MARTÍNEZ; A. KESELMAN; M.E. RODRÍGUEZ; I. BERGADÁ; H.G. JASPER; H.M. DOMENÉ; M.G. ROPELATO

Cartagena de Indias

Congreso; XXII Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP); 2011

Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)

Growth Hormone Receptor Gene (GHR) Heterozygous Variants in Idiopathic Short-Statured (ISS) Children Selected According to IGF-I and GH-binding Protein (GHBP) Levels M.G. Ballerini1, P. Scaglia2, A. Martinez2, A. Keselman1, M.E. Rodriguez1, I. Bergadá, H.G. Jasper2, H.M. Domené2, M.G. Ropelato1 ¹Divisón de Endocrinología, Centro de Investigaciones Endocrinológicas, Hospital de Niños, Ricardo Gutiérrez, Buenos Aires-Argentina Introduction: Previous studies showed heterozygous GHR gene variants in about 5?8% of children with ISS. Aim: To determine the prevalence of GHR gene variants in ISS children selected according to IGF-I and GHBP serum levels. Methods: From 61 prepubertal ISS children (height < SD, height velocity < 10centile, normal GH response after Arginine-Clonidine test), 14 (5 familial/8 non-familial, 1 unknown) were selected presenting, IGF-I (extractive-RIA) < .50 and GHBP (in house immunofluorometric assay) either < .0 SDS (n = 13) or >+2.0 SDS (n = 1). Coding exons and intronic flanking regions of GHR gene were PCR-amplified, purified and sequenced. These GHR gene variants were also screened in 25 normal subjects. Results: Previously reported common SNPs were found in all 14 ISS children: rs12521020 (Intron-1), rs10941579 (Intron-2), rs6179 (Exon-6), rs33972388 (Intron-7), rs2973015 (Intron-8), rs6180 (Exon-10). In addition, 3/5 familial ISS children presented uncommon SNPs in heterozygosis (Table). Conclusion: Adequate selection criteria (low IGF-I and either low or high GHBP levels) may improve the identification of carriers for GHR gene variants (3/14, 20%) in children with ISS. Interestingly, all these variants were found only in familial ISS children. However, the biological effect of these variants on GH sensitivity remains to be determined.