Second tier test for the diagnosis of Angelman syndrome. Order if suspicion for Angelman syndrome remains after normal methylation analysis. For first-tier testing, refer to Angelman Syndrome and Prader-Willi Syndrome by Methylation (2005077).
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA) or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: Developmental delays by 6-12 months of age, seizures, microcephaly, movement or balance disorder, minimal or absent speech, and a unique behavioral phenotype which includes a happy demeanor with frequent laughter, hand flapping, and excitability.
Prevalence: 1 in 15,000.
Inheritance: Varies, depending upon the molecular genetic mechanism. UBE3A mutations identified by sequencing may be maternally inherited or de novo. Offspring of a female carrier of a UBE3A sequence mutation are at 50 percent risk for AS.
Penetrance: Paternally inherited UBE3A sequence mutations are asymptomatic.
Cause: Absence of maternal expression of the UBE3A gene.
Molecular Genetic Mechanisms: Microdeletions of the AS/PWS critical region (68 percent), UBE3A mutations (11 percent), paternal uniparental disomy of chromosome 15 (7 percent), imprinting center defects (3 percent), unbalanced chromosome translocation (less than 1 percent), and unknown (11 percent).
Clinical Sensitivity: 11 percent.
Methodology: Bidirectional sequencing of the UBE3A coding region and intron-exon boundaries.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations, and large deletion/duplications will not be detected. Other molecular mechanisms resulting in Angelman syndrome will not be assessed.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|2005565||Angelman Syndrome (UBE3A) Seq Specimen||31208-2|
|2005566||Angelman Syndrome (UBE3A) Seq Interp||35291-4|