TRANSLATIONAL RESEARCH IN PRADER-WILLI SYNDROME AND OBESITY - PART I

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 Prader-Willi综合征（PWS）是一种复杂的神经行为综合征，其主要临床特征包括肥胖、摄食过多、张力减退、认知障碍、独特的行为表型和新生儿发育不良。 这种综合征是最常见的肥胖遗传原因。遗传缺陷已定位于染色体15 q11-q13的2兆碱基区域。它是一种连续基因综合征，几个基因的表达缺失导致完整的表型。据推测，该区域中一个基因的表达缺失可能导致PWS的一些但不是全部特征（即，“PWS-like”）。在过去的10年里，我们已经提到了我们的遗传诊所的病态肥胖儿童的数量来评估PWS。这些儿童中的一些在临床上和分子上没有PWS，但我们注意到他们似乎都有一定程度的认知障碍，并且他们与PWS有其他相似之处（即，PWSlike）。 因此，我们假设早发性病态肥胖和认知障碍之间存在关系。发育延迟可能是由于各种神经递质或其他生化标志物的有害影响，如在各种新生儿生化疾病如苯丙酮尿症（PKU）中所见。因此，我们希望通过使用心理测量测试以及评估包括神经递质在内的各种生化参数来记录和量化PWS和PWS样个体中认知障碍的程度和类型。此外，我们打算将PWS和PWS样个体之间的各种生化参数以及认知障碍的程度相关联。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Prader-Willi syndrome (PWS) is a complex neurobehavioral syndrome whose main clinical features include obesity, hyperphagia, hypotonia, cognitive impairment, a distinct behavioral phenotype and neonatal failure-to thrive. This syndrome is the most commonly recognized genetic cause of obesity. The genetic defect has been localized to a 2 megabase region of chromosome 15q11-q13. It is a contiguous gene syndrome with the loss of expression of several genes resulting in the complete phenotype. It is postulated that a loss of expression of one gene in this region may lead to some, but not all the features of PWS (i.e., "PWS-like"). For the last 10 years we have had referred to our Genetics clinics a number of morbidly obese children to evaluate for PWS. A number of these children clinically and molecularly do not have PWS, but we have noted that they all seem to have some degree of cognitive impairment and that they have other similarities with PWS (i.e., PWSlike). Thus we have hypothesized that there is a relationship between early onset morbid obesity and cognitive impairment. The developmental delay may be due to harmful effects of various neurotransmitters or other biochemical markers such as seen in various neonatal biochemical diseases such as phenylketonuria (PKU). Thus we would like to document and quantify the degree and types of cognitive impairment in PWS and PWS-like individuals by the use of psychometric testing as well as assess various biochemical parameters including neurotransmitters. In addition, we intend to correlate various biochemical parameters between the PWS and PWS-like individuals as well as the degree of cognitive impairment.