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Comprehensive Peroxisomal Genes NGS Panel

Genes:
ACOX1;
AGPS;
AGXT;
AMACR;
CAT;
DNM1L;
GNPAT;
HSD17B4;
PEX1;
PEX2;
PEX3;
PEX5;
PEX6;
PEX7;
PEX10;
PEX12;
PEX13;
PEX14;
PEX16;
PEX19;
PEX26;
PHYH;
SCP2;
TRIM37

Syndrome Information

Clinical Description

This panel provides an comprehensive molecular assessment across multiple phenotypes.  Discrimination between most of these dirorders is 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.

Phenotypes covered by this panel include: 
     Zellweger Syndrome
     Neonatal Adrenoleukodystrophy
     Neonatal Refsum Disease and Adult Refsum Disease
     Rhizomelic Chondrodysplasia Punctata, Types 1, 2, and 3
     Peroxisomal Beta-Oxidation Defects
     and several rare single peroxisomal enzyme defects

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 several NGS panels for peroxisomal disorders.

Clinical Utility

Discrimination between multiple peroxisomal disorders when biochemical analysis is unclear or unavailable;  identification of causative mutations in known or highly suspicious cases; facilitate targeted carrier testing of relatives of proband and/or predictive prenatal testing.

Clinical Sensitivity

The clinical sensitivity of this panel is dependent on the phenotype of the patient and the genes in which pathogenic variants are reported.  The following are general clinical sensitivity ranges:  Acatalasemia:  >98%; AMACR deficiency: >98%; Mulibrey Nanism: <10%; Primary hyperoxaluria type 1:  >97%; Rhizomelic Chondrodysplasia Punctata:  >98%; Refsum Disease: >98%; Zellweger Spectrum Disorder:  >98%; Peroxisomal ß-oxidation defects:  >98%. For more detailed clinical sensitivity information, please see the individual panel web pages.

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).

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

Sequencing:  5-6 weeks

Fee and CPT Codes

NGS Panel:  $4104 for routine testing
CPT Code:  81479 x 24

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 several 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.