4.7 Article

Partial Primary Deficiency of Insulin-Like Growth Factor (IGF)-I Activity Associated with IGF1 Mutation Demonstrates Its Critical Role in Growth and Brain Development

期刊

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 94, 期 10, 页码 3913-3921

出版社

ENDOCRINE SOC
DOI: 10.1210/jc.2009-0452

关键词

-

资金

  1. Agence Nationale de la Recherche
  2. Universite Pierre et Marie Curie (UPMC), Assistance Publique Hopitaux de Paris
  3. Direction de l'Hospitalisation et de l'Organistion des Soins/Mission de L'observation, de la Perspective et de la Recherche [243/25.0505]
  4. UPMC

向作者/读者索取更多资源

Context: IGF-I is essential for fetal and postnatal development. Only three IGF1 defects leading to dramatic loss of binding to its type 1 receptor, IGF-1R, have been reported. Patient: We describe a very lean boy who has intrauterine growth restriction and progressive postnatal growth failure associated with normal hearing, microcephaly, and mild intellectual impairment. He had markedly reduced concentrations of IGF-I, with IGFBP-3 and ALS serum levels in the upper normal range or above. IGF-I serum concentrations differed according to the immunoassay used. A higher than average GH dose was required for catch-up growth. Given the mismatch between IGF-I and IGFBP-3 levels, we sequenced his IGF1 gene. Result: We identified a homozygous missense IGF1 mutation. This causes the replacement of a highly conserved amino acid (arginine 36) by a glutamine (R36Q) in the C domain of the predicted peptide. We showed that the abnormal IGF-I peptide has reduced mitogenic activity and partial loss of binding to its receptor IGF-1R. The patient's IGF-I level was undetectable in a highly specific monoclonal assay but elevated in a polyclonal assay. Conclusion: This first report of mild deficiency of IGF-I activity demonstrates that the integrity of IGF-I signaling is important for normal growth and brain development. Molecular defects leading to partial loss of IGF-I activity may not be uncommon in patients born small for gestational age. The characterization of this complex phenotype and identification of such molecular defects have therapeutic implications, particularly now that, in addition to GH, recombinant IGF-I is available for clinical use. (J Clin Endocrinol Metab 94: 3913-3921, 2009)

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据