PWSA (USA) Funded Research - December 2007

GENETIC UNDERPINNINGS OF RESTRICTED REPETITIVE BEHAVIOR -- principal investigator is Soo-Jeong Kim, M.D.

Expected Significance
Despite its clinical significance, little is known about underlying neurobiological mechanisms of restricted repetitive behavior (RRB) in PWS. Restricted Repetitive Behavior is an umbrella term used to describe a wide variety of maladaptive repetitive behaviors, such as stereotypy, self-injurious behavior (i.e., skin picking, nail biting, etc.), obsessions/compulsions, rituals/insistence on sameness behaviors, and restricted interests. The majority of individuals with Prader-Willi syndrome (PWS) suffer from clinically significant RRB that are impairing and often serve as focal points of interventions. RRB is also a diagnostic feature of Autism Spectrum Disorders (ASDs). Increased rates of ASDs have been reported among individuals with PWS. As PWS is caused by a structural or functional absence of paternally inherited genes in the 15q11-q13 region, specific genetic variants in the 15q11-q13 region may play a critical role in the clinical manifestation of RRB in individuals with PWS. In addition, abnormal serotonin (5-HT) neurotransmission may contribute to RRB in PWS, as selective serotonin reuptake inhibitors (SSRIs) have been used to treat certain RRB features with moderate degree of success.

The researchers have hypothesized that specific genetic variants in the 15q11-q13 region contribute to the risk of specific forms of RRB, and that interactions between genes within the 15q11-q13 region and the 5-HT system genes would increase the susceptibility to specific forms of RRB. They will also be investigating genotype-phenotype correlations, and examining gene-gene interactions.

Findings from this research project will lead to new treatment for this debilitating clinical condition (RRB) in individuals with Prader-Willi syndrome (PWS). This study will also generate data that may help to understand underlying genetic mechanisms for ASDs whose prevalence rate is significantly high in PWS. In addition, this project will provide an opportunity to test the hypothesis of gene-gene interactions among the 15q11-q13 region, SLC6A4 and TPH2. We believe the new knowledge from this project will ultimately benefit the scientific and clinical community of PWS.

edited:08/19/2008