• Test Code:
    2405
  • Department:
  • Test Synonyms:
    CDKL5CNTNAP2FOXG1IQSEC2MBD5MECP2MEF2CMEIS2 NRXN1SLC9A6TCF4UBE3AWDR45ZEB2
  • CPT Code(s):
    81406
Background:

Rett and Angelman syndromes and phenotypically related disorders are a class of neurodevelopmental conditions. Clinically these phenotypes may include intellectual delay/regression, seizures, and developmental delay. Typically Rett syndrome is seen in girls but Angelman syndrome has no gender bias. These conditions are typically inherited in an autosomal dominant, recessive or X-linked manner. Angelman syndrome is caused by mutations in the gene UBE3A, however due to genomic imprinting and only the maternal copy is active in the brain. Mutations in MECP2 are associated with Rett syndrome. Given this, methylation status of this genomic region should be considered for Angelman syndrome cases to assess paternal contribution or uniparental disomy.

Reasons for Referral:

  • Molecular confirmation for conditions related to Rett or Angelman syndrome
  • Carrier testing
  • Positive family history

Methodology:

Component 1: Next generation sequencing will analyze the exons or coding regions of 14 Rett-Angelman-associated genes using Illumina NextSeq 500 technology and preparing samples using hybridization probes to enrich exonic regions. Promoter, intronic, etc. regions are not assessed here but may contain variants that impact gene function.

Component 2:  A customized CytoSure “exon-centric” array (Oxford Gene Technology) will be used to detect deletions and duplications.  The targeted array has enhanced probes targeted to the exonic regions of 13 Rett-Angelman-associated genes.  The arrays are run using Agilent SureScan technology.

Rett-Angelman Syndrome Panel (14 genes):
CDKL5, CNTNAP2, FOXG1, IQSEC2, MBD5, MECP2, MEF2C, MEIS2, NRXN1, SLC9A6, TCF4, UBE3A, WDR45, ZEB2

Specimen Requirements:

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

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

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: 10µg at a minimum of 60-100ng/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:

8 weeks

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. GeneReviews : Angelman Syndrome http://www.ncbi.nlm.nih.gov/books/NBK1144/
  2. GeneReviews: MECP2-Related Disorders http://www.ncbi.nlm.nih.gov/books/NBK1497/

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.

Learn More