The comprehensive analysis of single and double-targeted mutagenesis of the genes encoding IGF-I, IGF-II and the type 1 IGF receptor demonstrated the critical role that these genes play in embryonic development [9-11]. The clinical studies of patients with genetic defects in the GH-IGF axis support the crucial role that IGF-I plays, not only in fetal growth but also in postnatal growth by mediating some of the growth-promoting effects of GH. The absence of circulating IGF-I as described in our patient and previously in patients with Laron syndrome has demonstrated the importance of circulating IGF-I in the feedback control of GH secretion [22,26]. Our studies have also shown that the absence of a functional IGF-I gene is compatible with life, but has marked effects in prenatal and postnatal linear growth and a significant impact in metabolic homeostasis, diminishing insulin sensitivity. The investigation of the IGF-I gene in children with severe growth retardation has expanded over the years [27,28]. Recent studies have investigated the association of possible genetic variations of the IGF-I gene with birth size (small for gestational age) in different populations [29,30]. Although the initial study did not find an association between IGF-I polymorphisms and birth size, a more recent study has shown transmission disequilibrium of two alleles in two different markers of the IGF-I gene in children with short stature born small for gestational age . Therefore, allelic variance of the IGF-I gene may play a role in both prenatal and postnatal growth. Finally, the unravelling of genes in the GH-IGF system and their protein structures has enabled us to improve the diagnosis of IGF-I deficiency at the molecular level and to use appropriate doses of IGF-I treatment in affected individuals.
- Growth hormone
- IGF-I system
- Insulin insensitivity
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism