Study on IGF-I insensitivity : Molecular study of type 1 IGF receptor gene

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Background : A recent report showed that the birth weight of type 1 insulin-like growth factor (IGF) receptor (IGF-IR) knockout mouse is about 45 % of that of wild type mouse. This suggests that anomalies in IGF-IR may cause intra-uterine growth retardation (IUGR) in human. Therefore, we analyzed the IGF-IR gene in patients with IUGR short stature.Subjects and Methods : We employed 21 IUGR short stature patients (IUGR group), 9 children born as IUGR but became normal height until 3 yr. old (catch-up group), and 18 normal adults (control group). The DNA of the patients and control subjects was analyzed for mutations in the gene for IGF-IR.Results : Deletion of 4 bp in 5'UTR region of exon 1 (977-980 delCTTT) was found in one patient. New silent mutation in exon 3 (204 CCC/CCT) was found in another patient. In addition we found three previously reported silent mutations, exon 11 (736 ACC/ACT) in nine patients ; exon 16 (1012 GAG/GAA) in 13 patients ; and exon 21 (1316 TAC/TAT) in two patients. In introns, two new single nucleotide mutations were found in intron 13 (-53 T/C in 12 patients) and in intron 15 (+72 A/G in nine patients). In intron 20, previously reported mutation (-34 G/A) was found in 11 patients. The incidence of the mutation in intron 13 was low in the catch-up group compared with IUGR and control groups.Conclusion : Four bp deletion in 5'UTR region of exon 1 was found in one patient. Next, we must analyze the IGF-IR gene of family members, and also study the function of this receptor. In addition to previously reported silent mutations, we also found new single nucleotide mutation in exon 3, intron 13, and 15. We will study the role of these single nucleotide polymorphism on antenatal growth as well as postnatal growth.