Prader-Willi/Angelman Methylation Studies
|Clinical info||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.|
|Associated Tests||FISH analysis for Prader-Willi/Angelman syndromes, Uniparental disomy studies for chromosome 15, UBE3A sequencing, 2nd Tier Rett/Angelman Panel|
|Detection||Methylation for Prader-Willi/Angelman syndromes will detect mutations in nearly all patients with Prader-Willi syndrome and approximately 78% of patients with Angelman syndrome.|
|Specimen Requirements||5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml|
|Transport||The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. 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.|
|Turnaround time||3 weeks|
|Prenatal testing||Prenatal diagnosis for Prader-Willi syndrome and Angelman syndrome via methylation studies are not available. However, deletion studies and UPD testing may be ordered when appropriate. 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.|
Molecular Diagnostic Lab
The Molecular Diagnostic Lab offers DNA analysis for many genetic disorders via gene sequencing, targeted mutation analysis, MLPA deletion/duplication testing, trinucleotide repeat analysis and next generation sequencing panels.