Prader-Willi Syndrome Methylation-Specific MLPA

Turnaround Time

3 weeks

CPT Code(s)

81331

Cost

$600

• Prader-Willi syndrome

Prader-Willi syndrome is an example of a disorder involving imprinted genes. Imprinted genes are only expressed from either the maternally or paternally derived member of a homologous chromosome pair. Prader-Willi syndrome is characterized by significant infantile hypotonia and feeding difficulties. In early childhood this transitions into excessive eating and morbid obesity. Developmental delay and behavioral problems are common features. Physical characteristics include hypogonadism, short stature, small hands and feet, almond shaped eyes, and hypopigmentation. Prader-Willi syndrome is caused by the lack of expression of the paternally derived region of chromosome 15 (15q11.2-q13). This lack of expression can be caused by a deletion of the paternal chromosome, maternal uniparental disomy (UPD) of chromosome 15 or more rarely, a defect in the imprinting region.

Methylation testing and copy number status is useful to confirm the diagnosis. Further testing is necessary to determine the etiology of the disorder and to allow for carrier testing and prenatal diagnosis.

A methylation sensitive multiplex ligation-dependent probe amplification (MLPA) assay is used to determine methylation status at 15q11.2-q13 as well as any copy number variants in this region. If an abnormal methylation pattern is identified, then pyrosequencing is performed to quantify the methylation at these sites as needed.

Methylation analysis for Prader-Willi/Angelman syndromes will detect nearly all cases of Prader-Willi syndrome and approximately 78% of patients with Angelman syndrome.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

Prenatal diagnosis is available if the familial mutations are known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.