Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum via the PEX6 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
7231 PEX6 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7231PEX681479 81479 $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 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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 the 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).

PEX6, a cytosolic protein, interacts with PEX1 and plays an important role in vesicle fusion and import of peroxisomal proteins. After PEX1, PEX6 is the second most affected gene among patients with PBD-ZSS (approximately 11-16%). Reported PEX6 pathogenic variants are scattered throughout all coding exons but commonly found in exon 1, including missense, nonsense, splicing site mutations, small deletion/insertions, and large deletions (Steinberg et al. 2004; Waterham and Ebberink 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

In two separate cohorts of PBD-ZSS patients, 11-16% of affected patients were identified with causative PEX6 variants (Zhang et al. 1999; Waterham and Ebberink 2012; Steinberg et al. 2004).

Clinical sensitivity for del/dup testing is expected to be low, but non-zero. Three PEX6 multi-exon deletions have been reported so far (Ebberink et al. 2010; Grønborg et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the PEX6 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 PEX6.

Gene

Official Gene Symbol OMIM ID
PEX6 601498
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Acyl-CoA Oxidase Deficiency via the ACOX1 Gene
Fetal Concerns Panel

Citations

  • Ebberink MS, Kofster J, Wanders RJA, Waterham HR. 2010. Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients. Hum. Mutat. 31: E1058–1070. PubMed ID: 19877282
  • 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
  • Grønborg S, Krätzner R, Rosewich H, Gärtner J. 2011. Lymphoblastoid cell lines for diagnosis of peroxisome biogenesis disorders. JIMD Rep 1: 29–36. PubMed ID: 23430824
  • 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
  • Zhang Z, Suzuki Y, Shimozawa N, Fukuda S, Imamura A, Tsukamoto T, Osumi T, Fujiki Y, Orii T, Wanders RJ, Barth PG, Moser HW, et al. 1999. Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders. Hum. Mutat. 13: 487–496. 

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.

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


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