• Test Code:
    2101
  • Department:
  • Test Synonyms:
    NBIA NGSATP13A2C19orf12COASYCPDCAF17FA2HFTLFUCA1KIF1AKMT2B (MLL2)PANK2PLA2G6SCP2SCL39A14SQSTM1TRIM32VPS13AWDR45
  • CPT Code(s):
    81479x18
Background:

Neurodegeneration with Brain Iron Accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration.  The age of onset ranges from infancy to late adulthood, and the rate of progression varies. Cognitive decline occurs in some subtypes, but more often cognition is relatively spared. Cerebellar atrophy is a frequent finding in some subtypes. The diagnosis is usually suspected with findings of brain iron accumulation on MRI.  However, both clinical findings and molecular genetic testing establish the diagnosis of specific subtypes.

Our panel is the most comprehensive clinical NBIA testing panel currently available. It includes the 10 genes associated with well-described NBIA disorders, as well as genes associated with new emerging phenotypes and related disorders. The results of each NBIA panel are reviewed by Dr. Susan Hayflick, who discovered many of these genes, and provides consultation on NBIA disorders to physicians around the world.

Reasons for Referral:

  • Confirmation of a suspected clinical diagnosis in patients with the hallmark findings of NBIA.
  • Further assessment of patients with clinical diagnosis of idiopathic NBIA who have had mutations ruled out in other genes.

Methodology:

Next generation sequencing will analyze the exons or coding regions of 18 NBIA-associated genes 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.

The 18 NBIA-associated genes are listed below:

ATP13A2  C19orf12  COASY CP   DCAF17 FA2H 
 FTL  FUCA1 KIF1A   KMT2B (MLL2)  PANK2  PLA2G6
 SCP2  SLC39A14  SQSTM1  TRIM32  VPS13A  WDR45

Panel Options:

  • Sequencing Only
  • Deletion/Duplication Only*
  • Sequencing AND Deletion/Duplication*

*Deletion/Duplication analysis not available for the gene KMT2B (MLL2)

Specimen Requirements:

Genomic DNA: 10 µg at a minimum concentration of 100 ng/µL needed

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

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

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:

8 weeks

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. Gregory A. and Hayflick S., 2014. GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK121988/

    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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