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 or mental retardation, 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 and 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
  • Mental retardation, Developmental delay
  • Hypogonadism
  • 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)

Sample Requirements

  • Infants: Two to three mL whole blood in purple top EDTA tube
  • Children (>2 years) and adults: five to seven mL whole blood in purple top EDTA tube

Sample Handling

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].

Shipping Address

Center for Human Genetics Laboratory
10524 Euclid Ave, Sixth Floor
Cleveland, OH 44106
216-983-1134

For local samples, please call the Center for Human Genetics Laboratory (216-983-1134) to arrange for sample pick up.

Turnaround Time

Seven to 14 days

List Price/CPT Codes

$220.50 / 81331

Please submit a completed Prenatal and Postnatal Cytogenetics and Molecular specimens requisition (PDF) for each sample.

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