Epilepsy and Seizure Disorders: Sequencing and Deletion/Duplication Panel
  • Overview
  • How to Order Test
  • Specimen Requirements
  • Test Description
  • Related Tests
  • Special Instructions
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Name
Epilepsy and Seizure Disorders: Sequencing and Deletion/Duplication Panel
Synonyms
Seizures, Seizure Disorders
Test Code
MEPI1
Indication
This test is indicated for individuals with epilepsy.
CPT Codes
81228 (x1), 81404 (x1), 81405 (x1), 81406 (x1)
Turn around time
12 weeks
Submit only 1 of the following specimen types
Type Specimen Requirements Specimen Collection and Shipping
Whole BloodIn EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Ship sample at room temperature with overnight delivery.
Isolated DNAIn microtainer: 60 ug

Isolation using the QiagenTM Puregene kit for DNA extraction is recommended.
Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.
Condition Description
Epilepsy is defined as a disorder in which an individual has recurrent, unprovoked seizures.  It has a prevalence of about 5-10 per 1000 people.  While the causes of epilepsy are diverse, a significant proportion are considered to be genetic in origin.  Epilepsy can occur as part of a clinical spectrum that is associated with a particular genetic syndrome, such as Mowat Wilson syndrome, Dravet syndrome, and “chromosomal” epilepsies.  Common “chromosomal” epilepsies include 1p36 deletion syndrome, Wolf-Hirschhorn syndrome, Angelman syndrome, Miller-Dieker syndrome, 15q inversion-duplication, Down syndrome and ring chromosome 14 and 20.  In addition, epilepsy can occur as an isolated finding, 40% of which are believed to be due to genetic causes.  Approximately 2% of the genetic causes of isolated epilepsy are due to monogenetic causes while the rest are thought to be due to multifactorial genetic and environmental causes.  Of the monogenetic genes identified, the majority code for ion channel subunits and neurotransmitter receptors.    

The epilepsy and seizure disorders panel is comprised of a next generation sequencing (NGS) and deletion/duplication panel testing for syndromic and non-syndromic causes of seizures.  We recommend that individuals with seizures have a chromosomal microarray as a first tier test.  Please click here for information on our EmArray Cyto and CytoScan SNP Array. Please note that the panel does not include deletion/duplication analysis for all genes on this panel. Please refer to the Methodology for a complete list of those genes. 

Support for the development of this panel was provided, in part, by a grant from the Epilepsy Foundation to Dr. Andrew Escayg, Associate Professor, Department of Human Genetics.

References:  
  • Michelucci et al., (2012), Curr Neurol Neurosci Rep, 12:445-455.
  • Nicita et al., (2012), Seizure, 21:3-11.
  • Pal et al., (2010), Nat Rev Neurol, 6:445-453.
  • Pandolfo, (2011), Semin Neurol, 31:506-518.
  • Poduri and Lowenstein, (2011), Curr Opin Genet Dev, 21:325-332.
Genes
Methodology
Next Generation Sequencing: In solution hybridization of all coding exons contained in the genes of the Epilepsy and Seizure Disorders Panel is performed on the patient's genomic DNA. Direct sequencing of the amplified captured regions is performed using next generation sequencing. The patient's gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger sequenced in order to confirm variants and ensure 100% coverage of the targeted exons. Sequence variations are classified as pathogenic variants, benign variants unrelated to disease, or variants of unknown clinical significance. Variants of unknown clinical significance may require further studies of the patient and/or family members. This assay does not interrogate the promoter region, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications.


Deletion/Duplication Analysis:  DNA isolated from peripheral blood is hybridized to a gene-targeted CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes that cover the entire genomic region. Please note that the following genes do not have deletion/duplication analysis included in this panel:  BCKDK ,CPA6, DNAJC5, GOSR2, GPR98, KCNT1, KCTD7, LIAS, SCARB2, SCN2A, SLC19A3, ST3GAL3, ST3GAL5, TBC1D24, and TSEN54.


Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
Detection
Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's clinical/biochemical phenotype.

Analytical Sensitivity: ~99%

Deletion/Duplication Analysis:  Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.
Related Tests
  • CytoScan + SNP and EmArray Cyto
  • Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
  • Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.
Special Instructions

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