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 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 21 NBIA-associated genes using Illumina NextSeq 500/550 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 21 NBIA-associated genes. The arrays are run using Agilent SureScan technology.
The 21 NBIA-associated genes are listed below:
| ATP13A2 |
C19orf12 |
COASY |
CP |
DCAF17 |
FA2H |
FTL |
| FUCA1 |
KIF1A |
KMT2B (MLL4) |
MECR |
PANK2 |
PLA2G6 |
PSEN1 |
| SCP2 |
SLC39A14 |
SQSTM1 |
TRIM32 |
UBTF |
VPS13A |
WDR45 |
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 (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)
Blood: EDTA or ACD (Solution A or B):
- Adult: 5 mL
- Child: 5 mL
- Infant: 2-3 mL
Saliva: 2 ORAgene™ Saliva Collection Kits (OGR-500) used according to manufacturer instructions. Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.
Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions. Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.
For routine testing of blood and saliva (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion. For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.
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:
- Gregory A. and Hayflick S., 2014. GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK121988/
Additional Info: