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Previous Volume 349:2211-2222 December 4, 2003 Number 23 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Perspective by Rosenfeld, R. G. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

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.

Source Information

From Cincinnati Children's Hospital Medical Center, Cincinnati (M.J.A., S.D.C.); the Hospital for Children and Adolescents (A.S., E.K., W.K., J. Klammt, R.P., K.R., B.S.) and the Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics ( J. Kratzsch), University of Leipzig, Leipzig, Germany; Genentech, San Francisco (A.G.); Institut Universitaire de Recherche Clinique, Montpellier, France (F.G., C.L.); and the Hallett Center for Diabetes and Endocrinology, Brown Medical School, Providence, R.I. (D.O., R.J.S.).

Drs. Abuzzahab and Schneider contributed equally to this article.

Address reprint requests to Dr. Chernausek at the Division of Endocrinology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, or at steven.chernausek{at}cchmc.org.

Full Text of this Article

Related Letters:

IGF-I Receptor Mutations and Intrauterine and Postnatal Growth Retardation
Unger S., Chernausek S. D., Kiess W., Smith R. J.
Extract | Full Text | PDF  
N Engl J Med 2004; 350:1362-1363, Mar 25, 2004. Correspondence

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