IGF 1 RECEPTOR MUTATIONS IN HUMAN INTRAUTERINE GROWTH RETARDATION

当胎儿在出生前发育减弱时，就会发生胎儿宫内发育迟缓。它类似于儿童时期的生长障碍，但由于在出生前准确评估间隔生长的情况很少，因此通常根据出生体重而不是生长速度来诊断它。这是一种常见的疾病，有多种原因，在所有怀孕中发生的比例高达3%。它与显著的疾病有关，如低血糖、智力缺陷和永久性矮小。虽然许多研究已经描绘了IUGR的临床谱系，并将一些病因和临床特征与预后联系起来，但在大多数情况下，IUGR的病因仍然未知，最终在人类中产生IUGR的确切机制几乎一无所知。因此，该项目的目标是通过确定IGF-1受体的异常是导致人类IUGR的原因来开始解决IUGR的问题。来自动物和人类的研究数据提供了确凿的证据，表明IGF-1作用的缺陷，无论是由于肽的产生减少，还是由于IGF-1受体的功能障碍，都可能导致人类的IUGR。

Intrauterine growth retardation ocurs when fetal growth is attenuated prior to birth. It is analogous to growth failure during childhood, but because there are so few instances when accurate interval growth is assessed prior to birth, it is usually diagnosed on the basis of birth weight rather than on rate of growth. It is a common disorder with multiple etiologies, occurring in up to 3% of all pregnancies. It is associated with significant morbidities, such as hypoglycemia, intellectual deficit, and permanent short stature. Although many studies have served to delineate the clinical spectrum of IUGR, and relate some of the etiologies and clinical features to outcome, in most cases, the causes of IUGR remain unknown and virtually nothing is known of the precise mechanisms which ultimately produce IUGR in humans. The objective of this project, therefore, is to begin to address the problem of IUGR by identifying abnormalities of the IGF-1 receptor as responsible for IUGR in humans. Data from animal and human studies provide solid evidence that a deficiency of IGF-1 action, either from reduced production of the peptide or dysfunction of the IGF-1 receptor, may lead to IUGR in man.