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Test Code UBE3Z UBE3A Gene, Full Gene Analysis

Useful For

Confirmation of a diagnosis of Angelman syndrome in patients who have previously tested negative by methylation analysis

Genetics Test Information

Testing includes full gene sequencing of the UBE3A gene

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

If skin biopsy is received, fibroblast culture will be added and charged separately.

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

Reporting Name

UBE3A Gene, Full Gene Analysis

Specimen Type


Shipping Instructions

Specimen preferred to arrive within 96 hours of draw.

Specimen Required

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.


Submit only 1 of the following specimens:


Specimen Type: Whole blood


Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated/Frozen


Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours


Specimen Type: Skin biopsy

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Reject Due To

No specimen should be rejected.

Clinical Information

Angelman syndrome (AS) is characterized by significant developmental delay and mental retardation, ataxia, jerky arm movements, unprovoked laughter, seizures, and virtual absence of speech. AS has several known genetic causes.


About 65% to 80% of affected individuals have a de novo deletion of essentially the same region of chromosome 15 detected for Prader-Willi syndrome (PWS): 15q11.2-13. The deletion can often be identified by high-resolution chromosome analysis in conjunction with FISH analysis. Molecular testing has shown that the AS deletion occurs only on the copy of chromosome 15 inherited from the mother. In about 5% of patients with AS, the affected individuals have inherited 2 copies of chromosome 15 from their father (paternal uniparental disomy) and no copies of chromosome 15 from their mother. Thus, the individuals with AS resulting from deletion or uniparental disomy are deficient for maternally derived genes from chromosomes 15. Deletions and uniparental disomy occur as de novo events during conception, so the recurrence risk to siblings is very low. Both of these genetic alterations, along with imprinting center defects (accounting for another 2%-5% of AS cases), cause an abnormal methylation pattern in the PWS/AS region of chromosome 15.


Another 10% of patients with AS have a documented mutation in the UBE3A gene located in the PW/AS region on chromosome 15. Mutations can either be maternally inherited in an autosomal dominant fashion or de novo. If the mutation is inherited, the risk to all future pregnancies is 50%. If testing of the affected individual's mother confirms she does not carry the mutation, the risk to future pregnancies is low but not zero, as cases of germline mosaicism have been reported. Individuals with a UBE3A mutation will display a normal methylation pattern.


No chromosomal or DNA abnormality has been identified in the remainder of clinically diagnosed AS patients (15%-25%). These patients may have genetic alterations that cannot be detected by current testing methods or alterations in as yet unidentified genes.


Initial studies to rule-out AS should include high-resolution cytogenetic analysis (CMS / Chromosome Analysis, for Congenital Disorders, Blood) to identify chromosome abnormalities that may have phenotypic overlap with AS, and methylation-sensitive, multiple ligation-dependent probe amplification (PWAS / Prader-Willi/Angelman Syndrome, Molecular Analysis) to identify deletions, duplications, and methylation defects. In cases where methylation analysis is negative, sequencing of the UBE3A gene may provide additional diagnostic information.

Reference Values

An interpretive report will be provided.


All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.


A small percentage of individuals who are carriers or have a diagnosis of Angelman syndrome caused by a UBE3A gene mutation may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of Angelman syndrome. For carrier testing, it is important to first document the presence of a UBE3A gene mutation in an affected family member.


In some cases, DNA alterations of undetermined significance may be identified.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.


Methylation analysis (PWAS / Prader-Willi/Angelman Syndrome, Molecular Analysis) is recommended prior to UBE3A gene analysis.

Method Description

Bidirectional sequence analysis is performed to test for the presence of a mutation in all coding regions and intron/exon boundaries of the UBE3A gene.(Unpublished Mayo method)

Day(s) and Time(s) Performed

Performed weekly, varies

Analytic Time

14 days

Specimen Retention Time

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81406-UBE3A (ubiquitina protein ligase E3A) (eg, Angelman syndrome), full gene sequence

Fibroblast Culture for Genetic Test

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)


LOINC Code Information

Test ID Test Order Name Order LOINC Value
UBE3Z UBE3A Gene, Full Gene Analysis In Process


Result ID Test Result Name Result LOINC Value
54034 Result Summary 50397-9
54035 Result In Process
54036 Interpretation 69047-9
54037 Additional Information 48767-8
54038 Specimen 31208-2
54039 Source 31208-2
54040 Released By No LOINC Needed


1. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions.

2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.