ANGELMAN SYNDROME, METHYLATION SUDIES
Gene: UBE3A (imprinted)
Chromosomal Locus: 15q11.2
Protein: Ubiquitin-protein ligase E3A
TURNAROUND TIME: 15 days
2012 AMA Code: 81331
TESTING METHODOLOGY: Methylation analysis
- 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 Amniocyte flasks. Maternal blood sample is required for maternal cell contamination studies. Direct specimens such as amniotic fluid or CVS cannot be tested.
Counseling and informed consent are recommended for genetic testing. A consent form
is available as a resource but not required.
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.
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
INDICATIONS FOR USE:
- Patients suspected of having Angelman syndrome based on clinical assessment