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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8527 WDR45 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8527WDR4581479 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

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.

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.

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the WDR45 gene account for 7% of Neurodegeneration with brain iron accumulation (Hogarth 2015).

Indications for Test

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.

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

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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.

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