Leukoencephalopathy with Vanishing White Matter and Ovarioleukodystrophy Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10205 EIF2B1 81479,81479 Order Options and Pricing
EIF2B2 81405,81479
EIF2B3 81406,81479
EIF2B4 81406,81479
EIF2B5 81406,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10205Genes x (5)81479 81405(x1), 81406(x3), 81479(x6) $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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

  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Variants in the genes that encode the five subunits of the eukaryotic translation initiation factor 2B (EIF2B1-B5) cause a heterogeneous spectrum of white matter disorders in which MRI studies show a symmetric pattern of white matter rarefaction, cystic degeneration, and loss of oligodendrocytes by apoptosis (van der Knaap et al. Neurology 51:540-547, 1998; Bugiani et al. J Neuropath Exp Neurol 69:987-996, 2010). Over the course of the disease, white matter gradually vanishes and is replaced by cerebrospinal fluid. Age at onset varies from prenatal to adulthood, with childhood onset being the most common. The earliest-onset cases are associated with oligohydramnios, IUGR, microcephaly, contractures, and severe encephalopathy. In later-onset cases development is normal initially, followed by a progressive course with features of ataxia, spasticity, optic atrophy, and diminished mental ability. Periods of acute deterioration can be provoked by stresses such as febrile illness, minor head injury or extreme fright (Vermeulen et al. Ann Neurol 57:560-563, 2005). A severe and early-onset form of the disease, called Cree leukoencephalopathy, is found among the native Cree and Chippewa populations of northern Quebec and Manitoba (Black et al. Ann Neurol 24:490-496, 1988). The mild juvenile and adult forms are often associated with primary ovarian failure, a syndrome referred to as ovarioleukodystrophy (Schiffmann et al. Ann Neurol 41:654-661, 1997; Fogli et al. Am J Hum Genet 72:1544-1550, 2003).

Genetics

The eukaryotic initiation factor, 2B, is a GTP exchange factor that regulates the rate of protein synthesis. EIF2B is a heteropentameric protein encoded by the five genes EIF2B1 – B5. The EIF2B-related leukodystrophies (OMIM 603896) are inherited in an autosomal recessive manner. Thus far, only EIF2B2, EIF2B4, and EIF2B5 have been implicated in ovarioleukodystrophy (Fogli et al. 2003). Approximately 90% of all pathogenic variants are missense variants (Fogli et al. Neurology 62:1509–517, 2004).

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity among individuals with characteristic MRI findings is ~90% (Schiffmann et al. GeneReview, 2010). Over 60% of all molecularly diagnosed patients have variants in EIF2B5 and another ~20% have variants in EIF2B2 or EIF2B4 (Schiffmann et al. 2010). Variants in EIF2B3 and EIF2B1 account for ~9% and ~2% of patients, respectively.

Testing Strategy

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

This panel provides 100% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Individuals with MRI findings demonstrating diffusely abnormal cerebral white matter.

Genes

Official Gene Symbol OMIM ID
EIF2B1 606686
EIF2B2 606454
EIF2B3 606273
EIF2B4 606687
EIF2B5 603945
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Leukoencephalopathy With Vanishing White Matter AR 603896

Related Test

Name
PGxome®

Citations

  • Black, D. N., et.al. (1988). PubMed ID: 3239951
  • Bugiani, M., et.al. (2010). PubMed ID: 20838246
  • Fogli, A., et.al. (2003). PubMed ID: 12707859
  • Fogli, A., et.al. (2004). PubMed ID: 15136673
  • Raphael Schiffmann, et.al. (2010).
  • Schiffmann, R., et.al. (1997). PubMed ID: 9153528
  • van der Knaap, M. S., et.al. (1998). PubMed ID: 9710032
  • Vermeulen, G., et.al. (2005). PubMed ID: 15786451

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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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