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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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7303 WWOX 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7303WWOX81479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Li Fan, MD, PhD, FCCMG, FACMG

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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