Test ID: UBE3Z UBE3A Gene, Full Gene Analysis, Varies
Useful For
Confirmation of a diagnosis of Angelman syndrome in patients who have previously tested negative by methylation analysis
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.
See Prader-Willi and Angelman Syndromes: Laboratory Approach to Diagnosis in Special Instructions.
Special Instructions
Method Name
Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis
Reporting Name
UBE3A Gene, Full Gene AnalysisSpecimen Type
VariesShipping 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 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
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 | Special Container |
---|---|---|---|
Varies | Varies |
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.
Interpretation
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.
Clinical Reference
1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424
2. Lossie AC, Whitney MM, Amidon D, et al: Distinct phenotypes distinguish the molecular classes of Angelman syndrome. J Med Genet 2001;38:834-845
3. Van Buggenhout G, Fryns JP: Angelman syndrome (AS, MIM 105830). Eur J Hum Genet 2009;17:1367-1373
4. Williams CA, Geaudet AL, Clayton-Smith J, et al: Angelman syndrome 2005: updated consensus for diagnostic criteria. Am J Med Genet 2006;140A:413-418
Day(s) and Time(s) Performed
Analytic Time
14 daysTest 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 | 94218-5 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
54034 | Result Summary | 50397-9 |
54035 | Result | 82939-0 |
54036 | Interpretation | 69047-9 |
54037 | Additional Information | 48767-8 |
54038 | Specimen | 31208-2 |
54039 | Source | 31208-2 |
54040 | Released By | 18771-6 |
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521) in Special Instructions.