title: Insulin-like growth factor I gene deletion causing intrauterine growth retardation and severe short stature.
abstract: The first human case of a homozygous molecular defect in the gene encoding insulin-like growth factor I (IGF-I) is described. The patient was a 15-year-old boy from a consanguineous pedigree who presented with severe intrauterine growth failure, sensorineural deafness and mild mental retardation. Endocrine evaluation of the growth hormone (GH)--IGF-I axis revealed elevated GH secretion, undetectable serum IGF-I and normal 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 truncated mature IGF-I peptide. This patient demonstrates that complete disruption of the IGF-I gene in man is compatible with life, and indicates a major role for IGF-I in human fetal growth. In addition, his neurological abnormalities suggest that IGF-I may be involved in central nervous system development.
authors.affiliation: University Department of Paediatrics, John Radcliffe Hospital, Oxford, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Woods
authors.forename: C
authors.initials: C
authors.lastname: Camacho-Hübner
authors.forename: D
authors.initials: D
authors.lastname: Barter
authors.forename: A J
authors.initials: AJ
authors.lastname: Clark
authors.forename: M O
authors.initials: MO
authors.lastname: Savage
mesh_terms: D000293:Adolescent; D003638:Deafness / Q000150:complications / Q000235:genetics; D005317:Fetal Growth Retardation / Q000150:complications / Q000235:genetics*; D017353:Gene Deletion; D006130:Growth Disorders / Q000235:genetics*; D019382:Human Growth Hormone / Q000097:blood / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000502:physiology; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics; D008297:Male; D008967:Molecular Biology; D010641:Phenotype
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I