• Test Code:
    1030
  • Department:
  • Test Synonyms:
    UBE3A full gene sequencingAngelman syndrome sequencing
  • CPT Code(s):
    81406
Background:

Angelman syndrome is a disorder characterized by severe developmental delay, a happy demeanor, limited speech and language, as well as abnormal gait and movement. This disorder is found in approximately 1 in 15,000 individuals, however it may be underdiagnosed as most of the clinical features do not manifest until 1 year of age or later. Molecular defects leading to Angelman syndrome involve absence or inactivation of the maternally inherited UBE3A allele and include abnormal DNA methylation, large deletions of the Angelman/Prader-Willi regulatory region, uniparental disomy, deletions of the Angelman syndrome imprinting control regions, as well as mutations in UBE3A. Approximately 70% of molecular defects in Angelman syndrome are large deletions of 15q11.2-q13, uniparental disomy or deletions of the Angelman syndrome imprinting control region (approximately 10%), and no molecular defects are found in approximately 10% of individuals. Mutations in UBE3A cause approximately 10% of Angelman syndrome cases.

Reasons for Referral:

  • Suspected Angelman syndrome diagnosis with normal DNA methylation results
  • Carrier testing for relatives with an affected Angelman syndrome family member
  • Predispositional testing for asymptomatic children with an affected sibling or family member

Methodology:

Next generation sequencing will analyze the exons or coding regions of UBE3A using Illumina NextSeq 500 technology.  Samples are prepared using hybridization probes to enrich exonic regions.  Promoter, intronic, etc. regions are not assessed on our assay, but may contain variants that impact gene function.

OR

Sequencing for UBE3A is carried out by amplification of all exons and intron/exon boundaries followed by bi-directional Sanger sequencing.  The sensitivity of full gene sequencing is estimated to be approximately 99% for single nucleotide substitutions and small insertions/deletions.  All nucleotide changes are analyzed within the context of current databases and literature to predict pathogenicity.

Specimen Requirements:

Blood:  EDTA or ACD (Solution A or B):

    • Adult: 5mL
    • Child: 5mL
    • Infant: 2-3mL

Saliva: 2 ORAgene Saliva Kit(s) (OGR-500)
Skin Fibroblast: Punch Biopsy, or 2 T-25 confluent flasks
Prenatal:

  • Direct Amniotic Fluid (10-20mL)
  • Direct CVS
  • Cultured Amnio or CVS (2-T25 flasks)

DNA: 1-2µg at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

  • Maternal cell rule-out testing will be performed on all prenatal specimens received.Please provide maternal blood in addition to the fetal specimen.Additional charges apply for the maternal cell rule-out test.
  • All genetic testing performed on Direct CVS or Direct Amniotic Fluid specimens will be confirmed on cell cultures prepared by Knight Diagnostic Laboratories.Cell cultures will be prepared from the specimen received.Additional charges apply for confirmatory testing.

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

21 days

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

  1. Clayton-Smith, J et al. Angelman syndrome: a review of the clinical and genetic aspects. J Med Genet 2003; 40: 87-95.
  2. Tan, W et al. Angelman syndrome: Mutations Influence Features in Early Childhood. Am J Med Genet Part A 2010; 155: 81-90.
  3. Williams, C et al. Clinical and genetic aspects of Angelman syndrome. Genetics in Medicine 2010; 12(7): 385-395.
  4. Schneider M. et al, 2007 Clin Genet 72:30-38.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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