Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum via the DNM1L Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11249 DNM1L 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11249DNM1L81479 81479 $890 Order Options and Pricing

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

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

Turnaround Time

18 days on average

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

DNM1L encodes a member of the dynamin superfamily proteins mediating the division of both mitochondria and peroxisomes. Unlike typical PBD-ZSS, DNM1L pathogenic variants are reported to result in a lethal presentation in neonates characterized by defects in both mitochondria and peroxisomes. DNM1L-assocated diseases can be an autosomal dominant condition secondary to dominant-negative missense variants in the middle domain of the encoded protein (Waterham et al. 2007; Chang et al. 2010) or be a recessive disorder due to loss-of-function mutations (Yoon et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

DNM1L pathogenic variants appear to be very rare and have only been reported in two families to date (Waterham et al. 2007; Yoon et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the DNM1L 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

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 DNM1L.

Gene

Official Gene Symbol OMIM ID
DNM1L 603850
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Chang C-R, Manlandro CM, Arnoult D, Stadler J, Posey AE, Hill RB, Blackstone C. 2010. A lethal de novo mutation in the middle domain of the dynamin-related GTPase Drp1 impairs higher order assembly and mitochondrial division. J. Biol. Chem. 285: 32494–32503. PubMed ID: 20696759
  • 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
  • Waterham HR, Koster J, Roermund CWT van, Mooyer PAW, Wanders RJA, Leonard JV. 2007. A lethal defect of mitochondrial and peroxisomal fission. N. Engl. J. Med. 356: 1736–1741. PubMed ID: 17460227
  • Yoon et al. 2014. G.O.6. Neuromuscular Disorders 24: 794. PubMed ID: Abstract

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.
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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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