Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 21, Leipzig, Germany.
Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):191-206. doi: 10.1016/j.beem.2010.09.012.
Until 2003 monogenetic aberrations that lead to a child that is born too small for gestational age (SGA) were poorly defined. With the first report of mutations within the insulin-like growth factor type 1 receptor (IGF1R) gene in two non-syndromic patients born SGA, who failed to thrive despite normal or even elevated IGF1 serum concentrations the concept of IGF1 resistance has been established. The identification of additional individuals bearing IGF1R mutations along with comparative, genetic, structural and biochemical studies has provided evidence for the pathogenic impact of the IGF1R mutations on human longitudinal growth. However, the variability in the occurrence of additional clinical manifestations, such as developmental delay, might indicate that the pleiotropic functions of the IGF-IGF1R system are partially redundant. It is apparent that we have just begun to unravel the multifaceted IGF1R actions at the interface of growth control, maintenance of metabolic homeostasis and neurodevelopment and neural protection.
直到 2003 年，导致胎儿出生时体重小于胎龄（SGA）的单基因异常仍未得到明确定义。首次报道了两个非综合征性 SGA 患儿的胰岛素样生长因子 1 型受体（IGF1R）基因突变，尽管血清 IGF1 浓度正常甚至升高，这些患儿仍生长不良，从而确立了 IGF1 抵抗的概念。随着对 IGF1R 突变的其他个体的鉴定以及比较、遗传、结构和生化研究，为 IGF1R 突变对人类纵向生长的致病影响提供了证据。然而，其他临床表现（如发育迟缓）的发生存在变异性，这可能表明 IGF-IGF1R 系统的多效性功能部分冗余。显然，我们才刚刚开始揭示 IGF1R 在生长控制、维持代谢稳态和神经发育及神经保护的界面中的多方面作用。
