Early Infantile Epileptic Encephalopathy and Intellectual Disability via the SPTAN1 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 4249 | SPTAN1 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Early infantile epileptic encephalopathy 5 (EIEE5; OMIM: 613477) is characterized by infantile onset of epilepsy and moderate to severe intellectual disability. Patients present with severe hyoptonia as infants with onset of epilepsy at ~3 months of age; seizures are often refractory to antiepileptic medication. Psychomotor development is severely delayed, and patients exhibit intellectual disability with absence of language. Brain MRI reveals hypomyelination and reduction of subcortical white matter (Writzl et al. 2012). Patients with SPTAN1 variations may also be diagnosed with West syndrome, another infantile epileptic disorder characterized by hypsarrhythmia as revealed by EEG recordings (Nonoda et al. 2013).
Genetics
Cases of EIEE5 are sporadic and are caused by heterozygous de novo mutations in the SPTAN1 gene. Gain-of-function mutations, such as in-frame deletions and insertions, of SPTAN1 have been reported in patients with intractable epilepsy, hypomyelination and intellectual disability (Saitsu et al. 2010). Large deletions of SPTAN1 have also been reported and are associated with intellectual disability, but not reductions in white matter or severe epilepsy (Saitsu et al. 2010; Campbell et al. 2012).
SPTAN1 encodes an alpha spectrin subunit. Spectrin proteins assemble into heterodimers of alpha and beta subunits and act as submembranous scaffolds in neurons. Spectrins are required for proper localization of voltage gated sodium channels to synapses. Reported gain-of-function mutations in SPTAN1 disrupt heterodimer assembly and interfere with wild-type function of the spectrin protein (Saitsu et al. 2010).
Clinical Sensitivity - Sequencing with CNV PG-Select
Mutations in SPTAN1 were found in 1% (1 of 95) of patients with idiopathic intellectual disability (Hamdan et al. 2012).
Testing Strategy
This test provides full coverage of all coding exons of the SPTAN1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for SPTAN1 testing include patients with intractable infantile seizures, intellectual disability and severe hypomyelination of cerebral white matter.
Candidates for SPTAN1 testing include patients with intractable infantile seizures, intellectual disability and severe hypomyelination of cerebral white matter.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| SPTAN1 | 182810 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Epileptic Encephalopathy, Early Infantile, 5 | AD | 613477 |
Citations
- Campbell IM, Yatsenko SA, Hixson P, Reimschisel T, Thomas M, Wilson W, Dayal U, Wheless JW, Crunk A, Curry C, Parkinson N, Fishman L, et al. 2012. Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A. Genetics in Medicine 14: 868–876. PubMed ID: 22722545
- Hamdan FF, Saitsu H, Nishiyama K, Gauthier J, Dobrzeniecka S, Spiegelman D, Lacaille J-C, Décarie J-C, Matsumoto N, Rouleau GA. 2012. Identification of a novel in-frame de novo mutation in SPTAN1 in intellectual disability and pontocerebellar atrophy. European Journal of Human Genetics 20: 796–800. PubMed ID: 22258530
- Nonoda Y, Saito Y, Nagai S, Sasaki M, Iwasaki T, Matsumoto N, Ishii M, Saitsu H. 2013. Progressive diffuse brain atrophy in West syndrome with marked hypomyelination due to SPTAN1 gene mutation. Brain and Development 35: 280–283. PubMed ID: 22656320
- Saitsu H, Tohyama J, Kumada T, Egawa K, Hamada K, Okada I, Mizuguchi T, Osaka H, Miyata R, Furukawa T, Haginoya K, Hoshino H, et al. 2010. Dominant-Negative Mutations in ?-II Spectrin Cause West Syndrome with Severe Cerebral Hypomyelination, Spastic Quadriplegia, and Developmental Delay. The American Journal of Human Genetics 86: 881–891. PubMed ID: 20493457
- Writzl K, Primec ZR, Stražišar BG, Osredkar D, Pe?ari?-Megli? N, Kranjc BS, Nishiyama K, Matsumoto N, Saitsu H. 2012. Early onset West syndrome with severe hypomyelination and coloboma-like optic discs in a girl with SPTAN1 mutation: West Syndrome and SPTAN1. Epilepsia 53: e106–e110. PubMed ID: 22429196
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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ORDER OPTIONS
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