Angelman/Prader-Willi syndrome Methylation

Test Information

This test determines the level of methylation at CpG sites within the Angelman syndrome/Prader-Willi syndrome critical region on chromosome 15 via pyrosequencing.

Turnaround Time

3 weeks

CPT Code(s)

81331

Cost

$350

Clinical Information

Prader-Willi and Angelman syndromes are examples of disorders 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.
Angelman syndrome is characterized by significant developmental delay or intellectual disability, severe speech impairment, an ataxic gait, and inappropriate happy behavior including excessive laughing and smiling. Other physical concerns include microcephaly, seizures, wide mouth and a prominent mandible. Angelman syndrome is caused by the lack of expression of the maternally inherited region of chromosome 15 (15q11.2-q13). This lack of expression can be caused by a deletion of the maternal chromosome, paternal uniparental disomy (UPD), a mutation in the UBE3 gene in this region, or an imprinting defect.
Southern blot analysis using methylation sensitive restriction enzymes can determine whether the patient has both maternally derived and paternally derived material in the critical region of chromosome 15.

Indications

Methylation testing 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.

Methodology

Methylation analysis via pyrosequencing

Detection

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

Specimen Requirements

5 to 7 ml of peripheral blood collected in an EDTA (lavender top) tube is the preferred specimen type. The minimal blood needed for reliable DNA isolation is 3 ml. Extracted DNA is also accepted for this test.

Transport Instructions

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 Testing Information

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.

Have Questions Need Support?

Call our laboratory at 1-800-473-9411 or contact one of our Laboratory Genetic Counselors for assistance.
Robin Fletcher, MS, CGC
Kellie Walden, MS, CGC

Methylation Analysis, Molecular Testing, Other Molecular Testing
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Meet the Shenal Family

Our daughter, Ryleigh, was diagnosed with a rare chromosomal deletion shortly after she was born in 2010. Since we received her diagnosis, the Greenwood Genetic Center has become part of our family. They made certain that we did not feel alone, and they continue to provide ongoing, compassionate care for our child. The impact they have had on our family and others across the globe everyday is immeasurable. We can't imagine walking this journey without their...

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