• Test Code:
    2100
  • Department:
  • Test Synonyms:
    NBIA NGSATP13A2C19orf12COASYCPDCAF17FA2HFTLFUCA1KIF1AKMT2B (MLL4)PANK2PLA2G6SCP2SLC39A14SQSTM1TRIM32VPS13AWDR45
  • CPT Code(s):
    81479x1881228
Background:

Neurodegeneration with Brain Iron Accumulation (NBIA) is a group of neurodegenerative diseases caused by iron accumulation in the basal ganglia leading to progressive dystonia, parkinsonism, neurocognitive anomalies, and ophthalmologic disorders.  The age of onset varies from infancy to late adulthood, and progression can be rapid or slow with long periods of stability.  Ten types and their associated genes have been described.  Although cognition is usually spared, some cognitive decline has been reported in certain 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:

Component 1: 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.

Component 2:  A customized CytoSure “exon-centric” array (Oxford Gene Technology) will be used to detect deletions and duplications.  The targeted array has enhanced probes targeted to the exonic regions of 16 NBIA-associated genes.  The arrays are run using Agilent SureScan technology. 

The 1​8 NBIA-associated genes are listed below:

 ATP13A2  C19orf12  COASY CP  DCAF17  FA2H 
 FTL  FUCA1  KIF1A  KMT2B (MLL4)*  PANK2 PLA2G6
 SCP2*  SLC39A14  SQSTM1  TRIM32  VPS13A  WDR45

*not assessed for deletions/duplications

 Panel options offered by our laboratory:

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

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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