Diagnostic testing for Prader-Willi and Angleman syndromes: Report of the ASHG/ACMG Test and Technology Transfer Committee.

Overview Prader-Willi syndrome (PWS) is a complex disorder whose diagnosis may be difficult to establish on clinical grounds and whose genetic basis is heterogeneous. Slightly >70% of cases are due to a 15q11q13 deletion in the paternally contributed chromosome. These deletions are optimally detected by FISH utilizing SNRPN (small nuclear ribonucleoprotein N) and alpha-satellite DNA probes. Approximately 28% of cases of PWS are due to maternal uniparental disomy (UPD). This abnormality can best be documented using microsatellite probes. Less than 2% of cases have an abnormality in the imprinting process, which causes nonexpression of paternal genes in the PWS critical region. The latter group is detectable through identification of parent-of-origin differences by using methylation-sensitive SNRPN or PW71B probes, a process called methylation analysis. Chromosome analysis is usually a routine part of the evaluation of these patients, in order to rule out other abnormalities, and will also detect rare instances of tr anslocations or other chromosome rearrangements. Although high-resolution chromosome analysis will reveal many interstitial deletions, it is no longer considered sufficient.