IGF 1 RECEPTOR MUTATIONS IN HUMAN INTRAUTERINE GROWTH RETARDATION

宫内生长迟缓发生在胎儿出生前生长减弱。 它类似于儿童时期的生长失败，但由于在出生前评估准确的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绘了IUGR的临床谱，并将一些病因和临床特征与结果相关联，但在大多数情况下，IUGR的原因仍然未知，并且几乎不知道最终在人类中产生IUGR的确切机制。 因此，本项目的目标是通过鉴定导致人类IUGR的IGF-1受体异常来开始解决IUGR问题。来自动物和人类研究的数据提供了坚实的证据，即由于肽的产生减少或IGF-1受体功能障碍而导致的IGF-1作用的缺乏可能导致人类的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.