Expression of four genes between chromosome 15 breakpoints BP1 and BP2 in subjects with Prader-Willi Syndrome and impact on cognitive and behavioral measures

 Douglas C. Bittel, Jennifer Zarcone and Merlin G. Butler 

There are two distinct typical chromosome 15q deletion subtypes (type I and type II) in Prader-Willi syndrome (PWS). The larger type I (TI) typical deletion includes breakpoints BP1 and BP3 while the smaller type II (TII) typical deletion includes breakpoints BP2 and BP3. The effects of the two distinct deletion subtypes on clinical presentation are under investigation.  Four genes have been recognized between BP1 and BP2 and includes NIPA1, NIPA2, CYFIP1 and GCP5. It has been reported that these deleted genes may impact on cognition, behavior, and visual integration with poorer scores reported in those PWS individuals having the larger TI deletion.  Specifically, the most striking observation is the significant correlation of NIPA2 gene expression with adaptive behavior, academic achievement, and visual motor integration scores along with obsessive compulsive behaviors in PWS.  The purpose of this study is to better comprehend the importance of the four genes located between breakpoints BP1 and BP2 through gene expression studies and to better quantify the differences between the genetic subtypes.  A greater exploration into the contribution of these genes and their effect on cognition, behavior and neurological function along with the genetic subtypes of PWS will aid in a better understanding of the pathophysiology in PWS leading to treatment modalities.

edited: 08/19/2008