Molecular diagnosis of Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia and feeding problems in infancy, developmental delay, hyperphagia with obesity, short stature, hypogonadism, characteristic facial appearance, and behavior problems. The diagnosis of PWS is based on clinical findings that change with age. PWS has proved to be a difficult condition to recognize with the diagnosis often being delayed until later childhood or even adulthood. Therefore, a molecular testing for PWS is needed to confirm the diagnosis.

OBJECTIVE: To study the clinical features of Prader-Willi syndrome patients and confirm diagnosis by molecular testing.

MATERIAL AND METHOD: Eighteen Prader-Willi syndrome patients who were diagnosed between March, 1997 and February, 2002 at the Genetic Unit, Queen Sirikit National Institute of Child Health, Bangkok. Peripheral blood lymphocytes were obtained and cultured using the standard technique for chromosome analysis. For fluorescence in situ hybridization (FISH) studies, the specific DNA probes for loci small nuclear ribonucleoprotein polypeptide N (SNRPN) were used to detect deletion. Non-deleted cases were confirmed to have PWS by methylation analysis.

RESULTS: The diagnosis of eighteen PWS patients was confirmed by FISH using DNA probes for loci SNRPN demonstrating a deletion of chromosome 15q11-q13 in fourteen cases (77%). Four cases (23%) were confirmed to have PWS resulting from maternal uniparental disomy by demonstrating exclusively maternal specific DNA methylation patterns.

CONCLUSION: The clinical diagnosis of PWS should be confirmed by molecular testing especially in the infancy period to avoid needless invasive diagnostic testing.