Department of Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry London, UK.
Front Endocrinol (Lausanne). 2011 Dec 12;2:95. doi: 10.3389/fendo.2011.00095. eCollection 2011.
Human genetic defects in the growth hormone (GH)-IGF-I axis affecting the IGF system present with growth failure as their principal clinical feature. This is usually associated with GH insensitivity (GHI) presenting in childhood as severe or mild short stature. Dysmorphic features and metabolic abnormalities may also be present. The field of GHI due to mutations affecting GH action has evolved rapidly since the first description of the extreme phenotype related to homozygous GH receptor (GHR) mutations in 1966. A continuum of genetic, phenotypic, and biochemical abnormalities can be defined associated with clinically relevant defects in linear growth. The mechanisms of the GH-IGF-I axis in the regulation of normal human growth is discussed followed by descriptions of mutations in GHR, STAT5B, IGF-I, IGFALS, IGF1R, and GH1 defects causing bio-inactive GH or anti-GH antibodies. These GH-IGF-I axis defects are associated with a range of clinical, and hormonal characteristics. An up-dated approach to the clinical assessment of the patient with GHI focusing on investigation of the GH-IGF-I axis and relevant molecular studies contributing to the identification of causative genetic defects is also discussed.
人类生长激素（GH）-胰岛素样生长因子-I（IGF-I）轴中的遗传缺陷会影响 IGF 系统，其主要临床表现为生长障碍。这通常与 GH 不敏感（GHI）有关，在儿童期表现为严重或轻度身材矮小。还可能存在畸形特征和代谢异常。自 1966 年首次描述与 GH 受体（GHR）突变相关的纯合子 GH 受体（GHR）突变的极端表型以来，由于影响 GH 作用的突变导致的 GHI 领域发展迅速。与线性生长的临床相关缺陷相关，可以定义遗传、表型和生化异常的连续体。讨论了 GH-IGF-I 轴在调节正常人类生长中的机制，然后描述了 GHR、STAT5B、IGF-I、IGFALS、IGF1R 和 GH1 缺陷导致生物活性 GH 或抗 GH 抗体的突变。这些 GH-IGF-I 轴缺陷与一系列临床和激素特征有关。还讨论了更新的 GHI 患者临床评估方法，重点是对 GH-IGF-I 轴的调查以及有助于确定致病遗传缺陷的相关分子研究。
