PWSA (USA) Funded Research - Second Year March 2008

EXPRESSION OF FOUR GENES BETWEEN CHROMOSOME 15 BREAKPOINTS BP1 AND BP2 IN SUBJECTS WITH PRADER-WILLI SYNDROME AND IMPACT ON COGNITIVE AND BEHAVIORAL MEASURES
Investigators -- Douglas C. Bittel, Jennifer Zarcone and Merlin G. Butler

Second year approved – abstract on progress report on first year follows:

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder resulting from a paternal chromosome 15q11-q13 deletion in 70% of subjects, uniparental disomy 15 causes PWS in 25% of subjects and the rest are due to imprinting defects or chromosome 15 rearrangements. The deletion can be classified as either a large typical Type I (TI) deletion involving breakpoints BP1 and BP3 or a smaller typical Type II (TII) deletion involving breakpoints BP2 and BP3.

The researchers are working to quantify the expression of the four genes, NIPA1, NIPA2, CYFIP1 and GCP5 and correlate with neurodevelopmental parameters (behavioral, cognitive and visual integration measurements) previously reported to differ between the two deletion subtypes in Prader-Willi syndrome individuals. This project allows the investigators to expand their pilot data and analysis.

Preliminary analyses of their new data tend to support their hypothesis that changes in expression of these genes, whether due to genetics, epigenetics or chromosomal deletions result in alterations in the behavioral and cognitive parameters of individuals with PWS. They hypothesize that the size of the deletion should also be determined by using, for example aCGH technology, on each subject with the typical deletion to further characterize the size and type of the deletion. The enhanced gene expression patterns will then be correlated with behavior and clinical outcomes (and deletion size) in individuals with PWS. The gene expression patterns will also be compared with maternal disomy and comparison subjects.

edited:08/19/2008