Beta-propeller Protein-Associated Neurodegeneration (BPAN) via the WDR45 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 | |
|---|---|---|---|---|---|
| 8527 | WDR45 | 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
Beta-propeller protein-associated neurodegeneration (BPAN) was also described as static encephalopathy of childhood with neurodegeneration in adulthood (SENDA). Phenotypes include early onset global developmental delay during early childhood and development of Parkinsonism, dystonia, and dementia during adolescence or early adulthood. Seizures, spasticity and disordered sleep are also common features. Brain MRI reveals iron accumulation in the globus pallidus and substantia nigra. A characteristic finding is T1-weighted hyperintensity surrounding a central band of hypointensity in the substantia nigra. Cerebral and cerebellar atrophy are also present (Haack et al. 2012; Okamoto et al. 2014; Ozawa et al 2014; Hogarth 2015; Arber et al. 2016).
Genetics
Beta-propeller protein-associated neurodegeneration is inherited in an X-linked dominant manner and is caused by pathogenic variants in the WDR45 gene which encodes WD repeat-containing protein. This protein plays a putative role in the autophagy pathway, a lysosomal process to degrade cellular components such as damaged organelles, or protein aggregation (Okamoto et al. 2014; Arber et al. 2016).
The majority of patients are females, suggesting that beta-propeller protein-associated neurodegeneration is lethal in most males. However, in male patients, their phenotype is similar to that in females, indicating somatic mosaicism in surviving males. Females may also show mosaicism, as well as skewing of X chromosome inactivation (Haack et al. 2012; Arber et al. 2016).
Pathogenic variants in WDR45 for this disease cover missense, nonsense, small deletion/insertion, and splice variants, as well as large deletions in the WDR45 locus (Haack et al. 2012; Hayflick et al. 2013; Human Gene Mutation Database). These pathogenic variants can occur de novo.
Clinical Sensitivity - Sequencing with CNV PG-Select
Pathogenic variants in the WDR45 gene account for 7% of Neurodegeneration with brain iron accumulation (Hogarth 2015).
Testing Strategy
This test provides full coverage of all coding exons of the WDR45 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for this gene test include patients with symptoms suspicious for neurodegeneration with brain iron accumulation.
Candidates for this gene test include patients with symptoms suspicious for neurodegeneration with brain iron accumulation.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| WDR45 | 300526 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Neurodegeneration With Brain Iron Accumulation 5 | XL | 300894 |
Citations
- Arber C.E. et al. 2016. Neuropathology and Applied Neurobiology. 42: 220-41. PubMed ID: 25870938
- Haack T.B. et al. 2012. American Journal of Human Genetics. 91: 1144-9. PubMed ID: 23176820
- Hayflick S.J. et al. 2013. Brain : a Journal of Neurology. 136: 1708-17. PubMed ID: 23687123
- Hogarth P. 2015. Journal of Movement Disorders. 8: 1-13. PubMed ID: 25614780
- Human Gene Mutation Database (Bio-base).
- Okamoto N. et al. 2014. American Journal of Medical Genetics. Part A. 164A: 3095-9. PubMed ID: 25263061
- Ozawa T. et al. 2014. American Journal of Medical Genetics. Part A. 164A: 2388-90. PubMed ID: 25044655
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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