title: IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation.
abstract: BACKGROUND
  Approximately 10 percent of infants with intrauterine growth retardation remain small, and the causes of their growth deficits are often unclear. We postulated that mutations in the gene for the insulin-like growth factor I receptor (IGF-IR) might underlie some cases of prenatal and postnatal growth failure.
  
  
  METHODS
  We screened two groups of children for abnormalities in the IGF-IR gene. In one group of 42 patients with unexplained intrauterine growth retardation and subsequent short stature, we used single-strand conformation polymorphism analysis, followed by direct DNA sequencing of any abnormalities found. A second cohort consisted of 50 children with short stature who had elevated circulating IGF-I concentrations. Complete sequencing of the IGF-IR gene was performed with DNA from nine children. We also studied a control group of 43 children with normal birth weights.
  
  
  RESULTS
  In the first cohort, we identified one girl who was a compound heterozygote for point mutations in exon 2 of the IGF-IR gene that altered the amino acid sequence to Arg108Gln in one allele and Lys115Asn in the other. Fibroblasts cultured from the patient had decreased IGF-I-receptor function, as compared with that in control fibroblasts. No such mutations were found in the 43 controls. In the second group, we identified one boy with a nonsense mutation (Arg59stop) that reduced the number of IGF-I receptors on fibroblasts. Both children had intrauterine growth retardation and poor postnatal growth.
  
  
  CONCLUSIONS
  Mutations in the IGF-IR gene that lead to abnormalities in the function or number of IGF-I receptors may also retard intrauterine and subsequent growth in humans.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: M Jennifer
authors.initials: MJ
authors.lastname: Abuzzahab
authors.forename: Anke
authors.initials: A
authors.lastname: Schneider
authors.forename: Audrey
authors.initials: A
authors.lastname: Goddard
authors.forename: Florin
authors.initials: F
authors.lastname: Grigorescu
authors.forename: Corinne
authors.initials: C
authors.lastname: Lautier
authors.forename: Eberhard
authors.initials: E
authors.lastname: Keller
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klammt
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Doreen
authors.initials: D
authors.lastname: Osgood
authors.forename: Roland
authors.initials: R
authors.lastname: Pfäffle
authors.forename: Klemens
authors.initials: K
authors.lastname: Raile
authors.forename: Berthold
authors.initials: B
authors.lastname: Seidel
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Steven D
authors.initials: SD
authors.lastname: Chernausek
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002675:Child, Preschool; D018389:Codon, Nonsense; D015331:Cohort Studies; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006130:Growth Disorders / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010766:Phosphorylation; D017354:Point Mutation; D017526:Receptor, IGF Type 1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1