Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum via the PEX11B 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
15273 PEX11B 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15273PEX11B81479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Turnaround Time

18 days on average for standard orders or 13 days 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

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 several genes required for normal peroxisome assembly and/or peroxisomal protein import (Smith and Aitchison 2013). The clinical severity is generally correlated with the impact of a given mutation on peroxisome formation and function (Ebberink et al. 2011). PEX11B encodes PEX11-beta mediating peroxisome division and abundance. PEX11B pathogenic variants are one of the rare causes of PBD-ZSS. So far, only one PEX11B pathogenic variant (c.64C>T; p.Gln22*) was reported in one patient who presented with a PBD phenotype, but had normal PBD-related biochemical parameters (Ebberink et al. 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

Variants in PEX11B appear to be a rare cause of PBDs. So far, only one PEX11B pathogenic variant (c.64C>T; p.Gln22*) has been reported (Ebberink et al. 2012).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the PEX11B gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with clinical symptoms consistent with PBD-ZSS. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PEX11B.

Gene

Official Gene Symbol OMIM ID
PEX11B 603867
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Peroxisome Biogenesis Disorder 14B AR 614920

Citations

  • Ebberink MS, Koster J, Visser G, Spronsen F van, Stolte-Dijkstra I, Smit GPA, Fock JM, Kemp S, Wanders RJA, Waterham HR. 2012. A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11β gene. J. Med. Genet. 49: 307–313. PubMed ID: 22581968
  • 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
  • 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 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

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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