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Leukoencephalopathy with Vanishing White Matter and Ovarioleukodystrophy via the EIF2B2 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
EIF2B2 81405 81405,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8763EIF2B281405 81405,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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 platform).

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

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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.


Genetic Counselors


  • 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).


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 EIF2B2EIF2B4, 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 provides full coverage of all coding exons of the EIF2B2 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. 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. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in EIF2B2.


Official Gene Symbol OMIM ID
EIF2B2 606454
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Leukoencephalopathy With Vanishing White Matter AR 603896

Related Tests

Leukoencephalopathy with Vanishing White Matter and Ovarioleukodystrophy via the EIF2B1 Gene
Leukoencephalopathy with Vanishing White Matter and Ovarioleukodystrophy via the EIF2B5 Gene
Premature Ovarian Failure (POF) Panel


  • Black, D. N., et.al. (1988). "Leukoencephalopathy among native Indian infants in northern Quebec and Manitoba." Ann Neurol 24(4): 490-6. PubMed ID: 3239951
  • Bugiani, M., et.al. (2010). "Leukoencephalopathy with vanishing white matter: a review." J Neuropathol Exp Neurol 69(10): 987-96. PubMed ID: 20838246
  • Fogli, A., et.al. (2003). "Ovarian failure related to eukaryotic initiation factor 2B mutations." Am J Hum Genet 72(6): 1544-50. PubMed ID: 12707859
  • Fogli, A., et.al. (2004). "The effect of genotype on the natural history of eIF2B-related leukodystrophies." Neurology 62(9): 1509-17. PubMed ID: 15136673
  • Raphael Schiffmann, et.al. (2010). "Childhood Ataxia with Central Nervous System Hypomyelination/Vanishing White Matter."
  • Schiffmann, R., et.al. (1997). "Leukodystrophy in patients with ovarian dysgenesis." Ann Neurol 41(5): 654-61. PubMed ID: 9153528
  • van der Knaap, M. S., et.al. (1998). "Phenotypic variation in leukoencephalopathy with vanishing white matter." Neurology 51(2): 540-7. PubMed ID: 9710032
  • Vermeulen, G., et.al. (2005). "Fright is a provoking factor in vanishing white matter disease." Ann Neurol 57(4): 560-3. PubMed ID: 15786451


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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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