Diagnostic test for the Prader-Willi syndrome by SNRPN expression in blood.
BACKGROUND
Prader-Willi syndrome (PWS) is caused by alterations of the paternally derived chromosome 15 or by maternal uniparental disomy. The gene for the small nuclear ribonucleoprotein polypeptide N (SNRPN) is expressed only from the paternally derived chromosome 15, due to epigenetic imprinting. The SNRPN gene is not expressed in any patients with PWS regardless of the underlying cytogenetic or molecular causes.


METHODS
To develop a rapid molecular diagnostic assay for PWS, we tested the expression of the SNRPN gene and a control gene in 9 patients with PWS and 40 control individuals by PCR analysis of reverse transcribed mRNA from blood leucocytes. We then tested 11 blood samples from patients with suspected PWS.


RESULTS
SNRPN expression could readily be detected in blood leucocytes by PCR analysis in all control samples but not in samples from known PWS patients. Four suspected plus were negative for SNRPN expression were found to have chromosome 15 rearrangements, while the diagnosis of PWS was excluded in the remaining seven with normal SNRPN expression based on clinical, molecular, and cytogenetic findings.


CONCLUSIONS
The SNRPN-expression test is rapid and reliable in the molecular diagnosis of Prader-Willi syndrome.
Wevrick
R
R
Department of Genetics, Stanford University Medical Center, California 94305-5428, USA.
Francke
U
U
D001324:Autoantigens / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007231:Infant, Newborn; D016133:Polymerase Chain Reaction; D011218:Prader-Willi Syndrome / Q000175:diagnosis* / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear; D012680:Sensitivity and Specificity; D055517:snRNP Core Proteins
D001324:Autoantigens; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D055517:snRNP Core Proteins