• Test Code:
    1680
  • Department:
  • Test Synonyms:
    INADPLA2G6-Related Infantile Neuroaxonal DystrophySeitelberger DiseaseNBIAPLANAtypical NADDystonia-parkinsonism
  • CPT Code(s):
    81479x2
Background:

Infantile neuroaxonal dystrophy (INAD) is a progressive neurodegenerative disorder characterized by infantile or early childhood onset of progressive motor and sensory impairment; atypical INAD presents with later onset and a more protracted course (OMIM#256600).  INAD symptoms include regression, truncal hypotonia, spastic tetraparesis, mental retardation, optic atrophy and early death.  Common pathologic features include axonal degeneration with spheroid bodies throughout the central and peripheral nervous systems and cerebellar atrophy.  Some individuals with INAD show high brain iron accumulation in the globus pallidus.  The disease is autosomal recessive and caused by mutations in the PLA2G6 gene.


Reasons for Referral

  • Confirmation of clinical diagnosis in patients with classic or atypical INAD.
  • Testing of family members of INAD patients with known mutations.
  • Prenatal diagnosis of known familial INAD mutations.

Methodology:

The test has two components:

Component 1: Sequencing using either Sanger Sequencing or Next-Generation Sequencing. Sanger Sequencing:  Sequencing of PLA2G6 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 PLA2G6 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: Large deletions and duplications are assessed using either multiplex ligation-dependent probe amplification (MLPA) or by a customized CytoSure “exon-centric” array (Oxford Gene Technology).   The targeted array has enhanced probes targeted to the exonic regions of PLA2G6.  The arrays are run using Agilent SureScan technology.

Approximately 85% detection rate for patients whose finding meet diagnostic criteria for INAD.

Test reporting follows the American College of Medical Genetics (ACMG) guidelines.

Specimen Requirements:

Blood: EDTA (purple-top) or ACD (yellow-top) tube

  • Adult: 6.0 mL
  • Child: 3.0 mL
  • Infant: 2.0-3.0 mL

Prenatal:

  • Direct Amniotic Fluid (10-20mL)
  • Direct CVS
  • Cultured Amnio or CVS (2-T25 flasks) 

DNA: 10µg at a minimum of 100ng/µL

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

  • Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.
  • All genetic testing performed on Direct CVS or Amniotic Fluid specimens will be confirmed on cell cultures prepared by Knight Diagnostic Laboratories. Cell cultures will be prepared from the specimen received. Additional charges apply for confirmatory testing.

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:

INAD for Genetics Professionals

INAD for Primary Care Physicians

INAD Patient Brochure

Additional Info:

Custom sequencing of known familial mutations may be available; each request will be addressed given the specific parameters of each case.  Please call Client Services at (855) 535-1522 prior to submitting samples.

Prior to any genetic testing we recommend genetic counseling.  To receive forms and information about prenatal diagnostic testing, please contact Client Services.

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