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

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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.