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Zellweger Spectrum Disorders (ZSD) + Peroxisomal Beta-Oxidation Defects NGS Panel

Genes:
ACOX1;
DNM1L;
HSD17B4;
PEX1;
PEX2;
PEX3;
PEX5;
PEX6;
PEX10;
PEX12;
PEX13;
PEX14;
PEX16;
PEX19;
PEX26;
SCP2

Syndrome Information

Clinical Description

This is a compliation of panels for Zellweger spectrum disorders (ZSD) and Peroxisomal Beta-Oxidation defects.  Discrimination between these dirorders is usually possible through biochemical analysis; however, some patients have equivocal blood metabolite levels and may need further metabolic testing in cultured fibroblasts or DNA testing to make a final diagnosis.  

Additional clinical description is available on each disorder's page:
Zellweger Spectrum Disorders
Peroxisomal Beta-Oxidation Defects

Copies of the patient's biochemical analysis are extremely helpful in result interpretation.

Inheritance Pattern

Autosomal Recessive; Autosomal Dominant

Genotype-Phenotype Correlation

Missense mutations may be associated with milder clinical and biochemical phenotypes; however, this can be specific to certain mutations in certain genes

Test Information

Test Method

Next Generation Sequencing (NGS) of the coding regions and intron-exon boundaries of the listed genesDeletion/Duplication:  Dosage analysis by normalization of NGS read depth for the listed genes (except DNM1L); Sanger sequencing for potential fill in / confirmation 

This test is a compilation of two NGS panels for peroxisomal disorders.

Clinical Utility

Discrimination between ZSD and beta-oxidation defects; identification of causative mutations in known or highly suspicious cases of ZSD and/or Beta-oxidation defects based on clinical presentation and the blood biomarker profile; targeted carrier testing of relatives of proband; predictive prenatal testing when familial mutations are known. 

Clinical Sensitivity

This assay will detect at least one mutation in 99% of patients and two mutations in at least 98% of patients.

Analytic Sensitivity

> 99% for inherited single nucleotide and small insertion/deletion variants for the nucleotides evaluated; >99% for multi-exon deletions and >98% for single exon deletions; >90% for multi-exon duplications and >75% for single exon duplications. Lower limit of detection for single nucleotide variants: 25% allele frequency (>99% sensitivity).  There have been no reports of SCP2 deletions or duplications.  There have been individual case reports of deletions/duplications in multiple PEX genes, HSD17B4 and ACOX1, but no published case series.

Sample Requirements

3-6ml whole blood in EDTA (purple topped) tubes. (see Pediatric or Adult blood sample algorithms for additional information)

We prefer whole blood for all tests.

Turn Around Time

Approximately 4 weeks

Fee and CPT Codes

NGS Panel:  $3664 for routine testing
CPT Code:  81479 x 16

Special Considerations

 We request that copies of the patient's biochemical analysis be submitted with the sample.

Digenic inheritance (disease caused by mutations in 2 different PEX genes) has not been reported, but remains a theoretical possibility.  

This test is a compilation of two NGS panels for peroxisomal disorders.

INFORMED CONSENT from the patient is required prior to ordering a genetic test. The DNA Diagnostic Lab's consent is located on the second page of the requisition form. There is also a patient brochure, "Things Every Patient Should Know Before Consenting to a Genetic Test", available for download.