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

IGF-I不敏感性研究：1型IGF受体基因的分子研究

• 批准号: 12670751
• 负责人: KANZAKI Susumu
• 金额: $ 2.24万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670751/
• 关键词: insulin-like growth factor; IGF-I; IGF-receptor; IUGR; short stature; 胎内発育不全性低身長; 胎内発育遅延; 低身長; 成長ホルモン分泌不全症; GH-1遺伝子; 家族性

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.

工作背景：最近的报告显示，1型胰岛素样生长因子（IGF）受体（IGF-IR）敲除小鼠的出生体重约为野生型小鼠的45%。这表明IGF-IR异常可能会导致人类宫内生长迟缓（IUGR）。研究对象和方法：21例IUGR矮小症患者（IUGR组），其中9例出生时为IUGR，3岁时身高恢复正常。老年人（追赶组）和18名正常成年人（对照组）。结果：1例患者的IGF-1 R基因外显子1的5 'UTR区（977-980 delCTTT）有4个碱基缺失，缺失的突变位点为125 bp，缺失的突变位点为125 bp，缺失的突变位点为125 bp。另1例患者在外显子3发现新的沉默突变（204 CCC/CCT）。此外，我们发现了三个先前报道的沉默突变，9例患者的外显子11（736 ACC/ACT）; 13例患者的外显子16（1012 GAG/GAA）; 2例患者的外显子21（1316 TAC/达特）。在内含子中，在内含子13（12例患者中-53 T/C）和内含子15（9例患者中+72 A/G）中发现了两个新的单核苷酸突变。在内含子20中，在11例患者中发现了先前报道的突变（-34 G/A）。结论：在1例IUGR患者中发现外显子1的5 'UTR区有4个碱基缺失。下一步，我们必须分析家族成员的IGF-IR基因，并研究该受体的功能。除了以前报道的沉默突变，我们还发现了新的单核苷酸突变外显子3，内含子13和15。我们将研究这些单核苷酸多态性对产前生长以及产后生长的作用。

项目成果

Ikegami S, et al.: "An ultrasensitive assay revealed age-related changes in serum estradiol a low concentrations in both sexes from infancy to puberty"Clinical Endocrinology. (in press).

Ikegami S 等人：“超灵敏测定显示，从婴儿期到青春期，男女血清雌二醇浓度均呈低浓度，与年龄相关”临床内分泌学。

Kubo T,Takaiwa M,Kawakami M,Nagata K,Kanzaki S, et al.: "GH treatment in a patient with partial GH insensitivity syndrome."Clinical Pediatric Endocrinology. 9(1). 19-24 (2000)

Kubo T、Takaiwa M、Kawakami M、Nagata K、Kanzaki S 等人：“部分 GH 不敏感综合征患者的 GH 治疗。”临床儿科内分泌学。

Ikegani S: "An ultrasensitive assay revealed age-related changes in serum oestradiol at low concentrations in both sexes from infancy to puberty"Clinical Endocrinology. 55. 789-795 (2001)

Ikegani S：“超灵敏测定揭示了从婴儿期到青春期男女血清低浓度雌二醇的年龄相关变化”《临床内分泌学》。

Kubo T, Takaiwa M, Kawakami M, Nagata K, Nikaido K, Moriwake T, Kanzaki S, Seino Y.: "GH treatment in a patient with partial GH insensitivity syndrome"Clinical Pediatric Endocrinology. 9 (1). 19-24 (2000)

Kubo T、Takaiwa M、Kawakami M、Nagata K、Nikaido K、Moriwake T、Kanzaki S、Seino Y.：“部分 GH 不敏感综合征患者的 GH 治疗”临床儿科内分泌学。

神崎晋, 他: "新版ターナー症候群(この中の「骨代謝」の章を分担執筆した)"岡田義昭監修、メデイカルレビュー社. 9 (2001)

Susumu Kanzaki 等人：“新版特纳综合征（我合着了骨代谢章节”），由 Yoshiaki Okada 监督，医学评论出版 9 (2001)。