IGF-I Receptor Mutations Resulting in Intrauterine and Postnatal Growth Retardation

Two children with intrauterine growth retardation and short stature who had mutations in the gene for the insulin-like growth factor I receptor ( IGF-IR ) were identified among 51 children with short stature (most with intrauterine growth retardation) who were screened for these mutations. One child was a compound heterozygote for point mutations in exon 2, resulting in marked reductions in IGF-I–receptor binding. The other child had a nonsense mutation that reduced the number of cell-surface IGF-I receptors. No IGF-IR mutations were found in 43 controls with normal birth weights. Uncommon causes of intrauterine and postnatal growth failure. Insulin-like growth factors I (IGF-I) and II (IGF-II) are major regulators of somatic growth and cellular proliferation and act through a common receptor, the type I IGF receptor. The gene for the IGF-I receptor ( IGF-IR ) is homologous to the insulin receptor gene in terms of both exon and intron organization and its amino acid sequence (more than 50 percent identical). 1 Both encode precursor proteins that undergo post-translational modification to yield receptors composed of two α and two β subunits. The α subunits are extracellular, containing ligand-binding domains. The β subunits contain intracellular tyrosine kinase domains. 2 More than 50 . . .