Spinocerebellar Ataxia-12 via the WWOX 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 | |
|---|---|---|---|---|---|
| 7303 | WWOX | 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
Autosomal recessive spinocerebellar ataxia-12 (SCA12) is a childhood onset neurological disorder that shows features of ataxia and progressive myoclonic epilepsy. Patients present with generalized tonic-clonic seizures in the first year of life. Seizures may be well-controlled or intractable, depending on the severity of the disease (Gribaa et al. 2007; Abdel-Salam et al. 2014). EEG reveals bursts of sharp and slow waves. Psychomotor development is delayed in SCA12 patients; ataxic gait is evident when patients begin walking at 2-3 years of age, and patients have mild to severe intellectual disability (Gribaa et al. 2007). Other symptoms of SCA12 include uncontrolled coordination of hands, dysarthria, and nystagmus (Gribaa et al. 2007). EMG and muscle biopsy did not reveal significant findings (Gribaa et al. 2007). A family with severe SCA12 also showed neonatal growth defects, microcephaly, retinal degeneration, and death before two years (Abdel-Salam et al. 2014).
Genetics
SCA12 is inherited in an autosomal recessive manner and is caused by variants in the WWOX gene. Missense and nonsense variants in WWOX have been reported in SCA12 patients (Mallaret et al. 2014; Abdel-Salam et al. 2014).
WWOX encodes a protein with two WW domains and a short-chain dehydrogenase/reductase (SDR) domain. WWOX interacts with a variety of protein partners via its WW1 domain and is believed to function in multiple signaling pathways (Abu-Odeh et al. 2014). Antibody staining of tissue sections revealed WWOX expression in secretory epithelial cells as well as the cerebellum (Nunez et al. 2006). Rat strains homozygous for a frameshift variant in the WWOX gene have a lethal dwarfism with epilepsy phenotype, suggesting a conserved function of WWOX between rats and humans (Suzuki et al. 2009).
Clinical Sensitivity - Sequencing with CNV PG-Select
Screening of the WWOX gene in 189 patients with unexplained ataxia did not identify any WWOX variants, indicating that WWOX variants are a rare cause of ataxia (Mallaret et al. 2014).
Testing Strategy
This test provides full coverage of all coding exons of the WWOX gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
WWOX testing should be considered in patients with symptoms of SCA12, including infantile onset tonic-clonic seizures and gait ataxia, for which autosomal recessive inheritance is suspected. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in WWOX.
WWOX testing should be considered in patients with symptoms of SCA12, including infantile onset tonic-clonic seizures and gait ataxia, for which autosomal recessive inheritance is suspected. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in WWOX.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| WWOX | 605131 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Spinocerebellar ataxia, autosomal recessive 12 | AR | 614322 |
Citations
- Abdel-Salam G, Thoenes M, Afifi HH, Körber F, Swan D, Bolz H. 2014. The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration. Orphanet Journal of Rare Diseases 9: 12. PubMed ID: 24456803
- Abu-Odeh M, Bar-Mag T, Huang H, Kim T, Salah Z, Abdeen SK, Sudol M, Reichmann D, Sidhu S, Kim PM, Aqeilan RI. 2014. Characterizing WW Domain Interactions of Tumor Suppressor WWOX Reveals Its Association with Multiprotein Networks. Journal of Biological Chemistry 289: 8865–8880. PubMed ID: 24550385
- Gribaa M, Salih M, Anheim M, Lagier-Tourenne C, H’mida D, Drouot N, Mohamed A, Elmalik S, Kabiraj M, Al-Rayess M, Almubarak M, Betard C, et al. 2007. A new form of childhood onset, autosomal recessive spinocerebellar ataxia and epilepsy is localized at 16q21-q23. Brain 130: 1921–1928. PubMed ID: 17470496
- Mallaret M, Synofzik M, Lee J, Sagum CA, Mahajnah M, Sharkia R, Drouot N, Renaud M, Klein FAC, Anheim M, Tranchant C, Mignot C, et al. 2014. The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation. Brain 137: 411–419. PubMed ID: 24369382
- Nunez MI, Ludes-Meyers J, Aldaz CM. 2006. WWOX protein expression in normal human tissues. Journal of Molecular Histology 37: 115–125. PubMed ID: 16941225
- Suzuki H, Katayama K, Takenaka M, Amakasu K, Saito K, Suzuki K. 2009. A spontaneous mutation of the WWOX gene and audiogenic seizures in rats with lethal dwarfism and epilepsy. Genes, Brain and Behavior 8: 650–660. PubMed ID: 19500159
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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