Ordering Recommendation

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).

Mnemonic
UBE3A FGS
Methodology

Polymerase Chain Reaction/Sequencing

Performed

Varies

Reported

14-21 days

New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA) or yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval

By report

Interpretive Data

Background Information for Angelman Syndrome (UBE3A) Sequencing:
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.

Compliance Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81406

Components
Component Test Code* Component Chart Name LOINC
2005565 Angelman Syndrome (UBE3A) Seq Specimen 31208-2
2005566 Angelman Syndrome (UBE3A) Seq Interp 35291-4
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • UBE3A
Angelman Syndrome (UBE3A) Sequencing