Prader-Willi/Angelman Syndrome Methylation Studies
The Angelman (AS) and Prader-Willi syndromes (PWS) are distinct neurogenetic disorders caused by a deficiency of maternal (AS) or paternal (PWS) contributions for a specific region of chromosome 15. The affected genes are located in an imprinted region within 15q11-13. Clinically, these patients are distinguished by their clinical features. PWS patients classically have severe hypotonia and feeding difficulties in early infancy. Later in life, they have excessive eating and morbid obesity as well as developmental delay. AS patients classically have severe developmental delay, speech impairment, gait ataxia, microcephaly and seizures.
At the molecular level, paternal and maternal copies of this region can be distinguished by their differential methylation. Approximately 70 percent of PWS patients have a deletion on chromosome 15 detectable by cytogenetics and/or FISH. Another 28 percent of patients have maternal uniparental disomy for chromosome 15, and the remaining patients have an imprinting mutation. Methylation analysis will detect 99 percent of patients with PWS. Testing for PWS is offered as a panel which includes methylation analysis and blood chromosome analysis. Abnormal results are reflexed to FISH for deletion 15q11-15q13 and/or uniparental disomy as needed.
Approximately 70 percent of patients with AS have deletions of chromosome 15 detectable by cytogenetics and/or FISH. About 3 to 5 percent of patients have paternal uniparental disomy for chromosome 15 and another 5 percent have imprinting mutations. These abnormalities will be detected by methylation analysis. Patients with AS based on non-deletion/non-UPD mechanisms with normal imprinting at the SNRPN locus (~20 percent) will not be detected by this assay. Testing for AS is offered as a panel which includes methylation analysis an blood chromosome analysis. Abnormal results are reflexed to FISH for deletion 15q11-15q13 and/or uniparental disomy as needed.
Indications for Testing
- Hypotonia, poor sucking, and/or weak cry in infancy
- Developmental delay
- Abnormal eating habits and obesity in childhood
- Bouts of inappropriate laughter
- Lack of speech
- Early seizures
- Ataxia, broad-based gait
OMIM #s: 176270 (PWS) 105830 (AS)
- Infants: 2 – 3 mL whole blood in purple top EDTA tube
- Children (>2 years) and adults: 3 – 4 mL whole blood in purple top EDTA tube
Blood samples stored overnight should be refrigerated or kept cold. Blood samples should never be frozen. Specimens being sent from outside facilities should be packaged with a cold pack according to standard medical safety practices. The specimen should be shipped by overnight priority [scheduled to arrive by Friday morning at the latest].
Center for Human Genetics Laboratory
10524 Euclid Avenue, Sixth Floor
Cleveland, OH 44106
For local samples, please call Client Service (216-844-5227) to arrange for sample pick-up.
10 – 14 days
Please submit a completed Molecular Requisition (PDF) for each sample.