NGS Peroxisome Biogenesis Disorders Panel

 

Disorder Peroxisome Biogenesis Disorders (PBD)
Zellweger syndrome spectrum (ZSS)
Clinical info

Peroxisome biogenesis disorders are a result of peroxisomal fatty acid metabolism defect and constitute a spectrum of three phenotypes, Zellweger sydnrome, Neonatal adrenoleukodystrophy, and Infantile Refsum disease.  Zellweger  syndrome is the most severe and presents in the neonatal period with hypotonia, seizures, inability to feed,  characteristic facies, liver dysfunction, and specific skeletal findings.  These infants typically die within the first year of life.

Infantile Refsum disease, the least severe form, and neonatal adrenoleukodystrophy generally present later in infancy or early childhood.  Vision loss due to retinal dystrophy, sensorineural hearing loss, hypotonia, developmental delay, and episodes of hemorrhage or intracranial bleeding are all common features in later presentations.  Older children will typically have a slowly progressive disease.

PEX1

Zellweger; peroxisome biogenesis disorder 1A

PEX5  

 Peroxisome biogenesis disorder 2B

PEX12 

Peroxisome biogenesis disorder 3B

PEX6 

Zellweger; peroxisome biogenesis disorder 4A, 4B

PEX2

Zellweger; peroxisome biogenesis disorder 5A, 5B

PEX10

Zellweger; peroxisome biogenesis disorder 6A

PEX26

Peroxisome biogenesis disorder 7B

PEX16

Peroxisome biogenesis disorder 8B

PEX3    

Zellweger; peroxisome biogenesis disorder 10A

PEX13

Zellweger; peroxisome biogenesis disorder 11A

PEX19 

Zellweger; peroxisome biogenesis disorder 12A

PEX14 

Zellweger; peroxisome biogenesis disorder 13A

Indications

The clinical presentation for many of the peroxisome biogenesis disorders can be similar.  This panel may be useful in identifying the specific underlying genetic etiology. Specific genotype-phenotype correlations are established for some of the genes, so identifying the underlying molecular etiology may provide helpful information about the progression of the disease.
       
For patients with a specific suspected PBD, enzyme analysis or individual gene sequencing should be considered first.

Detection The current design of the lysosomal storage disease panel covers the coding region for all 12 genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations.

We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution testing whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.
Associated Tests

Effective January 1, 2017, all NGS panels are performed on an exome backbone with the potential for reflex to whole exome sequencing at a reduced cost. Please contact the laboratory to discuss the requirements for exome sequencing.

Specimen Requirements 5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred.  The minimal blood needed for reliable DNA isolation is 3 ml.
Transport The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.
Turnaround time 8-10 weeks
Prenatal testing If pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies.  Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.
CPT Codes 81479

Cost $3500

Insurance billing is available for this test. The Insurance Billing Form is required along with copies of the authorization or letter of agreement from the insurance company.

Contact For further information contact one of our This email address is being protected from spambots. You need JavaScript enabled to view it. at 1-800-473-9411.

Molecular Diagnostic Lab

The Molecular Diagnostic Lab offers DNA analysis for many genetic disorders via gene sequencing, targeted mutation analysis, MLPA deletion/duplication testing, trinucleotide repeat analysis and next generation sequencing panels.

Find out more