IGF 1 RECEPTOR MUTATIONS IN HUMAN INTRAUTERINE GROWTH RETARDATION

当胎儿在出生前生长减弱时，就会发生宫内生长迟缓。它类似于儿童时期的生长衰竭，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进行诊断。这是一种常见的疾病，有多种病因，发生在所有怀孕的3%。它与显著的发病率相关，如低血糖、智力缺陷和永久性身材矮小。尽管许多研究已经描述了IUGR的临床谱，并将一些病因和临床特征与结果联系起来，但在大多数情况下，IUGR的原因仍然未知，实际上对最终在人类中产生IUGR的确切机制一无所知。因此，本项目的目标是通过识别导致人类IUGR的IGF-1受体异常，开始解决IUGR问题。来自动物和人类研究的数据提供了确凿的证据，表明IGF-1作用的缺乏，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.