Angelman Syndrome

Test name:  Angelman Syndrome (AS) Testing
Also known as: Methylation 15, UBE3A gene sequencing, Deletion/duplication 15q11-q13 by FISH or microarray, Uniparental disomy (UPD) by UPD Array 


Indications:

  • Clinical features of AS include severe developmental delay or intellectual disability, significant speech impairment, and ataxic gait. Other common symptoms include seizures and microcephaly. Common behaviors include happy demeanor with frequent or inappropriate laughter and smiling. 
  • Prenatal and postnatal testing for at risk relative of and individual with a previously identified mutation in UBE3A

Test Information: AS is caused by abnormal or disrupted maternally imprinted UBE3A region within 15q11-q13. The combination of genetic testing offered at our laboratory, including methylation 15, UBE3A sequencing, UPD Array and deletion/duplication analysis will detect an abnormality for approximately 89-90% of individuals with AS. Approximately 10-11% of individuals with AS will not have an identifiable AS-causing genetic abnormality due to either incorrect clinical diagnosis or limitations of current methods of testing.

Name of Test Method Additional information
Methylation 15
  • Methylation specific PCR for the AS critical region following bisulfite modification of DNA
  • Approximately 72-78% of individuals with AS will have abnormal (positive) results
  • If methylation is positive consider Postnatal FISHUPD Array or 180K Microarray to determine if this abnormal result is due to deletion or UPD (imprinting center testing & MLPA not available at HGL)
  • If methylation is negative, consider UBE3A sequencing
UBE3A gene sequencing
(15q11-q13)
  • Gene sequencing of entire UBE3A coding region
  • If methylation is negative, approximately 11% of individuals with AS will have an identifiable mutation in UBE3A
  • If a patient’s mother has a UBE3A mutation, recurrence risk for siblings is 50% (refer to Familial Mutation Analysis)
Deletion/Duplication analysis
  • Approximately 68-70% of individuals with AS will have a deletion detected by FISH or array (180K Microarray or UPD Array) of the AS/PWS critical region
  • Recurrence risk is less than 1% with a deletion
Uniparental disomy (UPD) study
  • UPD Array will identify deletions of 15q11-q13 AND most whole-chromosome and segmental paternal UPD associated with AS
  • Approximately 7% of AS is due to paternal UPD plusit will detect deletions seen in 68-70% of individuals with AS
  • Recurrence risk is less than 1% with UPD or deletion
Chromosome Analysis
  • Less than 1% of individuals with AS have a chromosome arrangement involving the critical region of 15q11-q13
  • Often, the 5-7 Mb common AS deletion is not visible by routine chromosome analysis
  • Chromosome rearrangements are typically de novo but may be inherited; recurrence risk may vary depending on parental studies
Familial Mutation Analysis
  • Available if UBE3A mutation previously identified
  • If UBE3A mutation is identified for a child with AS, familial mutation analysis should be considered for the patient’s mother 
  • If a patient’s mother has a UBE3A mutation, recurrence risk for siblings is 50%

 


Additional tests available on postnatal samples (refer to additional pages for details):
Single gene testing – refer to Test Catalog for tests offered at HGL
Coming soon: Next Generation Sequencing (will include SLC9A6-Related Syndromic Mental Retardation [Angelman-Like Syndrome, X-Linked] and other genes with similar features) 


Specimen requirements:

  • One 2-5 ml whole blood sodium heparin (green top) tube AND one 2-5 ml whole blood EDTA (purple top) tube*
    *If newborn/limited blood – one sodium heparin (green top) tube with 1ml minimum

CPT codes:

  • Methylation: 83890(x4), 83891, 83892(x4), 83894(x4), 83896(x4), 83898(x2), 83900(x2)*
  • UBE3A sequencing: 83894, 83896(x10), 83898(x9), 83904(x18)*
  • Postnatal FISH for 15q11.2-q13 (SNRPN)*:
    • Age 0-3 months: 88230, 88271(x2), 88275, 88291
    • Age 3+ months: 88271(x1-3), 88272, 88275, 88291

*If concurrent G-bands studies are NOT being performed, add 88230

When requested, additional FISH testing will be performed and additional charges will be assessed. See the Postnatal FISH - including Rapid Aneuploidy FISH and/or Constitutional (Targeted) FISH page for a complete list of available tests.

  • 180K Microarray: 83892(x2), 88230, 88271(x16), 88386**
  • UPD Array: 83892(x2), 88230, 88271(x16), 88386**
  • Postnatal Chromosome Analysis: 88230(x2), 88261, 88280(x2), 88285(x3), 88289
  • Familial Mutation Analysis:  Contact the laboratory billing staff for current codes

**Unless using stored DNA from a prior sample, the following DNA Extraction codes (83891, 83894, 83907, 84311) will apply once for microarray/molecular testing.

Pricing: Contact the laboratory billing staff for current costs 


Shipping & Handling 

Required forms: Postnatal Test Request Form 

Turn-around time (times are estimates and may change with volume):

  • Methylation: 4 weeks
  • UBE3A sequencing: 4 weeks
  • Postnatal FISH: 7 days
  • 180K Microarray: 1-2 weeks
  • UPD Array: 1-2 weeks
  • Postnatal Chromosome Analysis: 7-10 days
  • Familial Mutation Analysis:  2 weeks

References: GeneReviews


revised 7-3-12

contact us
Phone:  402-559-5070 
1-800-656-3937 x95070
Fax:  402-559-7248
humangenetics@unmc.edu

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