• Test Code:
    1080
  • Department:
  • Test Synonyms:
    WDR45 full gene sequencingBPAN sequencingNBIA Sequencing
  • CPT Code(s):
    81479
Background:

Mutations in WDR45 are associated with beta-propeller protein-associated neurodegeneration (BPAN), an X-linked form of neurodegeneration with brain iron accumulation (NBIA). Patients with BPAN have characteristic brain MRI results (including T1 hyperintense and T2 hypointense signals in the substantia nigra), along with global developmental delay in childhood, regression in early adulthood, as well as progressive dystonia, parkinsonism and dementia. Additionally, patients with BPAN have similar phenotypic characteristics to individuals diagnosed with atypical Rett syndrome. If Rett specific mutations are not identified in those patients, WDR45 mutational analysis should be considered. All mutations in WDR45 are suspected to arise de-novo, however due to the X-linked nature of the gene females may have germline or somatic mutations while males will have somatic mutations.

Reasons for Referral:

  • Individuals with characteristic BPAN brain MRI results
  • Individuals identified with developmental delay accompanied by seizures and/or disordered sleep
  • Individuals identified with symptoms of atypical Rett syndrome

Methodology:

Sequencing can be performed by either Sanger Sequencing or Next-Generation Sequencing.

Sanger Sequencing: Sequencing of WDR45 is carried out by amplification of all exons and intron/exon boundaries followed by bi-directional Sanger sequencing. The sensitivity of full gene sequencing is estimated to be approximately 99% for single nucleotide substitutions and small insertions/deletions. All nucleotide changes are analyzed within the context of current databases and literature to predict pathogenicity.

NGS: Next generation sequencing will analyze the exons or coding regions of WDR45 using Illumina NextSeq 500 technology. Samples are prepared using hybridization probes to enrich exonic regions. Promoter, intronic, etc. regions are not assessed on our assay, but may contain variants that impact gene function.

Test reporting follows the ACMG Standards & Guidelines for Clinical Genetics Laboratories, Ultra-Rare Disorders Guidelines, and Interpretation of Sequence Variants Guidelines.

Specimen Requirements:

Blood:  EDTA or ACD (Solution A or B):    

    • Adult: 5 mL
    • Child: 5 mL
    • Infant: 2-3 mL

 DNA: 10µg at a minimum of 100ng/µL

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

14 - 21 days

Shipment Sensitivity Requirements:

Package and ship specimen to remain cold, but not frozen.  Ship via overnight express, using the FedEx priority overnight label provided. 
Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

1. Haack T, et al. Exome sequencing reveals de novo mutations in WDR45 causing a phenotypically distinct, X-linked dominant form of NBIA. 2012. AM J Hum Genet. 2102 Dec 7;91(6):1144-9.

2. Hayflick S, et al., BPAN: a new X-linked dominant form of neurodegeneration with brain iron accumulation (NBIA). Brain. 2013; 136(Pt6):1708-17.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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