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Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum via the PEX26 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
PEX26 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7787PEX2681479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum (PBD-ZSS) consist of three related diseases Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and Infantile Refsum disease (IRD) that share overlapping phenotypes with severity ranging from ZS to IRD. The overall incidence of PBD-ZSS is estimated to be from 1:500,000 to 1:50,000 (Steinberg et al. 2012). Common clinical features to all three include neurodevelopmental delay, glaucoma, retinal dystrophy, impaired hearing, renal cysts, and hepatic dysfunction (Wanders and Waterham 2005). Zellweger syndrome (ZS) is the most severe with neonatal onset, and characterized by typical craniofacial dysmorphism and profound hypotonia, severe seizures, and inability to feed. Infants with ZS usually do not make any developmental progress and rarely survive the first year of life. Compared to ZS, patients with NALD have less severe hypotonia and seizures during infancy and may reach school age. IRD is the least severe form. Patients with IRD show variable developmental delay and often present predominantly with vision problems, sensorineural hearing loss, and liver dysfunction. Most affected patients can reach childhood and, in rare cases, survive into adulthood. It has been suggested that a peroxisome biogenesis disorder should be considered in any individuals manifesting both vision and hearing problems. Biochemical findings of a PBD-ZSS patient include elevated plasma VLCFAs (C24:0 and C26:0), phytanic acid, and pipecolate and deficient plasmalogen synthesis in erythrocytes or cultured fibroblasts. A disparity of biochemical results obtained from different specimens (plasma, cultured cells or tissues) has been reported in milder patients due to peroxisomal mosaicism. Treatments of PBD-ZSS focus on symptomatic therapy (Steinberg et al. 2012; Steinberg et al. 2006).

Genetics

PBD-ZSS are all autosomal recessively inherited and caused by pathogenic variants in one of PEX genes required for normal peroxisome assembly and/or peroxisomal protein import. The clinical severity is generally correlated with the impact of a given mutation on peroxisome formation and function (Ebberink et al. 2011). At least 13 PEX genes have been reported to be involved with PBD-ZSS (Smith and Aitchison 2013).

PEX26 encodes a peroxisomal membrane protein interacting with PEX1 and PEX6. About 20 PEX26 pathogenic variants has been reported so far, which are commonly found in exons 2 and 3. The mutation spectrum includes missense, nonsense, splicing site mutations, small deletion/insertions, and a large deletion (Steinberg et al. 2004; Ebberink et al. 2011; Waterham and Ebberink 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

In a cohort of 1077 patients with PBD-ZSS, 45 patients (~4.2%) were identified with causative PEX26 mutations (Waterham and Ebberink 2012).

Clinical sensitivity for del/dup testing is expected to be low. A single gross deletion affecting exon 5 of PEX26 has been reported to be pathogenic (Matsumoto et al. 2003).

Testing Strategy

This test provides full coverage of all coding exons of the PEX26 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with clinical symptoms and biochemical findings consistent with PBD-ZSS. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PEX26.

Gene

Official Gene Symbol OMIM ID
PEX26 608666
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Acyl-CoA Oxidase Deficiency via the ACOX1 Gene

Citations

  • Ebberink MS, Mooijer PAW, Gootjes J, Koster J, Wanders RJA, Waterham HR. 2011. Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder. Hum. Mutat. 32: 59–69. PubMed ID: 21031596
  • Matsumoto N, Tamura S, Furuki S, Miyata N, Moser A, Shimozawa N, Moser HW, Suzuki Y, Kondo N, Fujiki Y. 2003. Mutations in novel peroxin gene PEX26 that cause peroxisome-biogenesis disorders of complementation group 8 provide a genotype-phenotype correlation. Am. J. Hum. Genet. 73: 233–246. PubMed ID: 12851857
  • Smith JJ, Aitchison JD. 2013. Peroxisomes take shape. Nat. Rev. Mol. Cell Biol. 14: 803–817. PubMed ID: 24263361
  • Steinberg et al. 2017. PubMed ID: 20301621
  • Steinberg S, Chen L, Wei L, Moser A, Moser H, Cutting G, Braverman N. 2004. The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. Mol. Genet. Metab. 83: 252–263. PubMed ID: 15542397
  • Steinberg SJ, Dodt G, Raymond GV, Braverman NE, Moser AB, Moser HW. 2006. Peroxisome biogenesis disorders. Biochim. Biophys. Acta 1763: 1733–1748. PubMed ID: 17055079
  • Wanders RJA, Waterham HR. 2005. Peroxisomal disorders I: biochemistry and genetics of peroxisome biogenesis disorders. Clin. Genet. 67: 107–133. PubMed ID: 15679822
  • Waterham HR, Ebberink MS. 2012. Genetics and molecular basis of human peroxisome biogenesis disorders. Biochim. Biophys. Acta 1822: 1430–1441. PubMed ID: 22871920

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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