Angelman Syndrome, Methylation Studies

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ANGELMAN SYNDROME, METHYLATION STUDIES

Gene: UBE3A (imprinted)

Chromosomal Locus: 15q11.2
 
Protein: Ubiquitin-protein ligase E3A
 
TURNAROUND TIME: 15 days
 
2012 AMA Code: 81331
 
TESTING METHODOLOGY: Methylation analysis
 
SPECIMEN REQUIREMENTS:
  • Collect: Prefer two 5ml whole blood EDTA (lavender top) tube.
  • Min. Collection: 0.7 ml whole blood EDTA.
  • Transport: Blood in EDTA at room temperature shipped regular next day air (No Saturday delivery; store specimen at 4°C and ship Monday).
  • Stability: Ambient: up to 7 days; Refrigerated: 2 weeks. Frozen: unacceptable
  • Unacceptable Conditions: Serum. Frozen or severely hemolyzed blood. Clotted blood.
  • Prenatal testing: Culture: Confluent T25 flask of Amniocytes or chorionic villi. Maternal blood sample is required for maternal cell contamination studies. Direct specimens such as amniotic fluid or CVS cannot be tested.
A Molecular Genetics Laboratory Test Requisition must accompany the specimen. Contact the Molecular Laboratory at 918-502-1721 to obtain further information.
 
Note: Counseling and informed consent are recommended for genetic testing. A consent form is available as a resource but not required.
 
INTERPRETATIVE DATA:
 
Prevalence: 1:12,000 to 1:20,000
 
Inheritance: Genomic imprinting; risk of recurrence depends on the genetic mechanism of loss of the maternally-contributed 15q11.2-q13 region (approximately 50% for imprint control defects or UBE3A mutations; <1% for deletions or UPD).
 
Disease Characteristics: Dysmorphic facial features, microcephaly, severe developmental delay, severe speech impairment, gait ataxia and a happy demeanor with frequent laughter.
 
Molecular Genetic Mechanism: The majority of patients (~70%) have interstitial deletions of the maternal chromosome 15q11.2-q13. Approximately 7% have paternal disomy (UPD), 3% have mutations of the imprint control region and 11% have point mutations in the UBE3A gene. In the remaining 10% of patients with AS, no molecular abnormality has been identified.
 
Related Tests: FISH, Angelman syndrome
 
Methods: Methylation-sensitive PCR using the 1st exon of the SNRPN gene.
 
Analytical Sensitivity: Methylation analysis detects 78% of individuals with Angelman syndrome.
 
Test Limitations: If test result is positive, further testing is required to identify the underlying molecular mechanism.
If test result is negative, sequencing of the UBE3A gene is recommended as this test does not detect UBE3A
mutations.
 
INDICATIONS FOR USE:
  • Patients suspected of having Angelman syndrome based on clinical assessment
ADDITIONAL RESOURCES: