CLINICAL CAPABILITIES // Genetic testing
Epilepsy
Identify genetic risk factors and causes of epilepsy.
About Genetic Testing for Epilepsy
Epilepsy is a chronic seizure disorder characterized by seizures that usually recur unpredictably in the absence of a consistent provoking factor. Most epileptic syndromes are genetically heterogeneous. Pathogenic variants in different genes cause the same syndrome in different individuals or families, and only a fraction of the potential genetic causes have been identified so far. Genetic assessment is enhanced when clinical information is available.
Although a positive test result can confirm or suggest that an individual has a specific syndrome, a negative test result might be uninformative. Fewer than one in five individuals with autosomal dominant nocturnal frontal lobe epilepsy have a pathogenic variant in any of the genes currently associated with that disorder.
In syndromes with incomplete penetrance and variable expressivity, a positive test result in an unaffected family member does not necessarily mean that the individual will develop epilepsy in the future, nor can it predict the specific phenotype if the individual does. An important example of this problem is genetic epilepsy with febrile seizures plus (GEFS+), in which some family members with a SCN1A variant remain unaffected, and phenotypes in affected family members vary from simple age limited febrile seizures to severe epileptic encephalopathies.
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Genetic testing may help identify the cause of a person's epilepsy
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It may lead to an accurate diagnosis and the best possible medical management
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It may be particularly helpful for individuals with genetic epilepsy disorders whose seizures are not well-controlled
How Do I Order a Test?
A printed copy of the requisition form must be submitted with the specimen if you are not placing your order through the online portal. You can find and print a copy of the requisition form here. If you need to modify your order, please contact client services.
Epilepsy Panel Best Practices
Preferred Specimen
2mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
Alternate Specimens
- Saliva
- Buccal swab
- gDNA
Let's get started!
How to Ship Your Samples
Follow IATA Regulations
Please note that Psomagen sample collection kits are built to protect the samples from being damaged during transport and to comply with the International Air Transport Association (IATA) regulation. If you are using packaging other than that provided by Psomagen, please make sure to follow the "three layers of packaging" rule to avoid the risk of having the package destroyed by the courier:
- A primary sample receptacle sealed (collection tube).
- A leak-proof specimen bag containing absorbent material.
- An outer packaging that meets the local postal regulations and is labeled as “Exempt Human Specimen.”
For more information please refer to page 187 of IATA Dangerous Goods Regulation.
Additional Shipment Requirements
For saliva, ship at room temperature (overnight shipping is not necessary).
For blood, we recommend using overnight shipping the same day that the blood is collected.
- Blood can be kept at room temperature for up to 48 hours.
- We request that blood is refrigerated no longer than two weeks.
- Please do not freeze blood as deletion/duplication analysis is not supported for frozen or partially frozen blood.
Please ship the specimen in a crush-proof container via FedEx Priority Overnight (in accordance with the FedEx Packaging Guidelines for Clinical Samples.
Our US Shipping Address
Attn: Clinical Laboratory Testing Personnel
Psomagen Inc.
1330 Piccard Drive, Ste 103
Rockville, MD 20850
Test for 46 related genes
Gene List
AMT
ARHGEF9
ATP1A2
CACNA1A
CDKL5
CHD2
CNTNAP2
DNM1
DOCK7
GABRA1
GABRG2
GLRA1
GRIN2A
GRIN2B
KCNQ2
KCNQ3
KCNT1
MEF2C
PCDH19
PNKP
PNPO
POLG
PRRT2
SCN1A
SCN1B
SCN8A
SCN9A
SLC2A1
SLC46A1
SLC9A6
SPTAN1
STX1B
STXBP1
SYNGAP1
SZT2
TBC1D24
TCF4
TPP1
TSC1
TSC2
ZEB2
Test Methodology and Limitations
DNA sequencing involves the extraction of genomic DNA from specimens collected in approved containers and provided the specimen meets required sample minimum quantity (e.g. volume, weight, etc.) this is followed by quantification and qualification to ensure the adequacy of amount and purity for sequencing. Subsequently, whole exome sequencing is conducted on an IlluminaTM short read sequencing (SRS) platform (e.g., NovaSeq X PlusTM) at Psomagen, Inc.’s laboratories (CLIA # 21D2062464, CAP # 8742212). DNA sequence alignment, variant calling, and variant filtering are performed utilizing the Illumina DRAGENTM bioinformatics pipeline (version 4.2.4.) and various tool sets, which align reads to the human reference genome (GRCh38) and identify single nucleotide variants (SNVs) and small insertions/deletions (InDels).
Variant annotations are performed using a pipeline available in Fabric Enterprise. Variant review and interpretation are conducted according to the standards and guidelines set forth by the American College of Medical Genetics and Genomics (Richards S, et al., Genet Med., 2015) by Fabric Clinical Labs (CLIA #45D2281059, CAP # 9619501). Only variants classified as pathogenic or likely pathogenic are reported. The following quality filters are applied to all variants: coverage <40x, allele balance outside 0.3-0.7.
Variants in the following genes are reported: ALDH7A1, AMT, ARHGEF9, ATP1A2, CACNA1A, CDKL5, CHD2, CNTNAP2, DNM1, DOCK7, FOLR1, GABRA1, GABRG2, GLRA1, GRIN2A, GRIN2B, KCNQ2, KCNQ3, KCNT1, MECP2, MEF2C, PCDH19, PNKP, PNPO, POLG, PRRT2, SCN1A, SCN1B, SCN2A, SCN8A, SCN9A, SLC2A1, SLC46A1, SLC9A6, SPTAN1, STX1B, STXBP1, SYN1, SYNGAP1, SZT2, TBC1D24, TCF4, TPP1, TSC1, TSC2, ZEB2
This test is designed to detect single nucleotide variants (SNVs) and small insertions/deletions (InDels). Next-Generation Sequencing (NGS) coverage may vary across the genome, potentially resulting in missed variants in regions with low coverage depth. Some genetic abnormalities may be undetectable with the current version of this test. While the DRAGEN bioinformatics pipeline demonstrates high accuracy for variant calling, there remains a possibility of false positive or false negative results due to variant interpretation which relies on current scientific knowledge and available databases. This may lead to the reclassification of reported variants as new information emerges from ongoing research and is updated in the ACMG guidelines. Furthermore, systematic chemical, computational, or human errors may contribute to false positives or false negatives of DNA variants. For any reported variants, confirmation by orthogonal technology and subsequent consultation with a genetic counselor or qualified healthcare provider can help to establish definitive risk. This result should be considered preliminary until such confirmation has been performed.
Clinical management for this individual should be based on personal and family history, along with other relevant information. If considered relevant to this individual’s clinical presentation and/or family history, targeted testing of appropriate family members of this individual for the reported variants may help to interpret these results. For assistance with the interpretation of these results, healthcare professionals may contact Psomagen directly at (301) 251-1007 or support@psomagen.com.
More Resources
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