OBJECTIVE: Prader-Willi syndrome (PWS) is an example of a human genetic disorder 
that involves imprinting genes on the proximal long arm of chromosome 15 and 
SNRPN gene as a candidate gene for this syndrome. The purpose of this study was 
to show the molecular genetic defects and genomic imprinting basis in Chinese 
PWS patients and to evaluate the clinical applications of a differential 
diagnostic test for PWS.
METHODS: Fluorescence in situ hybridization (FISH) and methylation-specific PCR 
(MSPCR) techniques were applied for 4 clinically suspected PWS patients. Using 
three probes, including SNRPN probe for identification of the critical locus in 
PWS region, D15Z1 and PML control probes for identification of the 15p arm and 
15q arm, the authors detected the deletions 15q in PWS. MSPCR was based on 
sodium bisulfite treatment of DNA and PCR primers specific for the maternal and 
paternal allele.
RESULTS: When hybridized with mixed probes, it was found in 2 patients that the 
central specific signal was absent, but both the flanking control signals were 
retained, indicating SNRPN gene deletion of chromosome 15q11-13. 
Bisulfite-modified DNA from all PWS children amplified with methylated 
allele-specific primer pair showed only maternal 131bp PCR product, indicating 
the maternal uniparental disomy (UPD15).
CONCLUSION: Genomic imprinting plays an important role in the molecular 
pathogenesis of PWS that caused by paternal microdeletions of 15q11-q13 or 
maternal UPD of chromosome 15. The basic defect seemed to be an absence of 
function of PWS genes that are normally expressed only from the paternal 
chromosome 15. MSPCR is a rapid and simple PCR-based assay compared with other 
cyto-molecular tests and its results were consistent with the clinical diagnosis 
of PWS, so it seems to be a reliable diagnostic method for PWS patients who show 
abnormal methylation at SNRPN. The genetic differential tests for PWS are 
important in determining familial recurrence risk.