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).
Polymerase Chain Reaction/Sequencing
Lavender (EDTA), pink (K2EDTA) or yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 1 mL)
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
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 Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.
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|