Angelman Syndrome (UBE3A) Sequencing
2005564
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
Within 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.





See Compliance Statement C: www.aruplab.com/CS
Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test; however, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
 
Note
 
CPT Code(s)
81406
Components
Component Test Code*Component Chart NameLOINC
2005565Angelman Syndrome (UBE3A) Seq Specimen31208-2
2005566Angelman Syndrome (UBE3A) Seq Interp35291-4
* 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