INSULIN-LIKE-GROWTH-FACTOR-I GENE DELETION CAUSING INTRAUTERINE GROWTH-RETARDATION AND SEVERE SHORT STATURE

The first human case of a homozygous molecular defect in the gene enco ding insulin-like growth factor I (IGF-I) is described. The patient wa s a 15-year-old boy from a consanguineous pedigree who presented with severe intrauterine growth failure, sensorineural deafness and mild me ntal retardation. Endocrine evaluation of the growth hormone (GH)-IGF- I axis revealed elevated GH secretion, undetectable serum IGF-I and no rmal serum IGF-binding protein-3, acid-labile subunit, and GH-binding activity. Analysis of the IGF-I gene revealed a homozygous partial IGF -I gene deletion involving exons 4 and 5, which encodes a severely tru ncated mature IGF-I peptide. This patient demonstrates that complete d isruption of the IGF-I gene in man is compatible with life, and indica tes a major role for IGF-I in human fetal growth. In addition, his neu rological abnormalities suggest that IGF-I may be involved in central nervous system development.