Prader-Willi syndrome (PWS) is a neurobehavioral disorder manifested by 
infantile hypotonia and feeding difficulties in infancy, followed by morbid 
obesity secondary to hyperphagia. It is caused by deficiency of paternally 
expressed transcript(s) within the human chromosome region 15q11.2. PWS patients 
harboring balanced chromosomal translocations with breakpoints within small 
nuclear ribonucleoprotein polypeptide N (SNRPN) have provided indirect evidence 
for a role for the imprinted C/D box containing small nucleolar RNA (snoRNA) 
genes encoded downstream of SNRPN. In addition, recently published data provide 
strong evidence in support of a role for the snoRNA SNORD116 cluster (HBII-85) 
in PWS etiology. In this study, we performed detailed phenotypic, cytogenetic, 
and molecular analyses including chromosome analysis, array comparative genomic 
hybridization (array CGH), expression studies, and single-nucleotide 
polymorphism (SNP) genotyping for parent-of-origin determination of the 15q11.2 
microdeletion on an 11-year-old child expressing the major components of the PWS 
phenotype. This child had an ∼236.29 kb microdeletion at 15q11.2 within the 
larger Prader-Willi/Angelman syndrome critical region that included the SNORD116 
cluster of snoRNAs. Analysis of SNP genotypes in proband and mother provided 
evidence in support of the deletion being on the paternal chromosome 15. This 
child also met most of the major PWS diagnostic criteria including infantile 
hypotonia, early-onset morbid obesity, and hypogonadism. Identification and 
characterization of this case provide unequivocal evidence for a critical role 
for the SNORD116 snoRNA molecules in PWS pathogenesis. Array CGH testing for 
genomic copy-number changes in cases with complex phenotypes is proving to be 
invaluable in detecting novel alterations and enabling better genotype-phenotype 
correlations.