DNA icon

Miller-Dieker Lissencephaly Syndrome via the YWHAE 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
YWHAE 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8893YWHAE81479 81479,81479 $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

Miller-Dieker lissencephaly syndrome (MDLS; OMIM 247200) is characterized by lissencephaly, microcephaly, wrinkled skin over the glabella and frontal suture, prominent occiput, narrow forehead, downward slanting palpebral fissures, small nose and chin, cardiac malformations, hypoplastic male external genitalia, growth retardation, and mental deficiency with seizures (Schinzel J Med Genet 25:454-462, 1988, Dobyns et al. Am J Hum Genet 48:584-594, 1991). Lissencephaly is defined as a "smooth brain" with absent gyri (agyria) or abnormally wide gyri (pachygyria) (Brakovich et al. Ann Neurol 1991; 30:139–46). MDLS patients mostly have more severe lissencephaly (complete agyria) than PAFAH1B1-associated lissencephaly patients (OMIM 607432), explained by the deletion of two additional genes, CRK and YWHAE (also known as 14-3-3ε), on 17p13.3 distal to PAFAH1B1 gene (Chong et al. Hum Molc Genet 6:147-155, 1997). Subsequently, it has been documented that the deletion of YWHAE gene is responsible for the greater severity of Miller-Dieker syndrome compared to PAFAH1B1-associated lissencephaly (Toyo-oka et al. Nat Genet 34:274-285, 2003).


Miller-Dieker lissencephaly syndrome is inherited as an autosomal dominant disorder. MDLS is caused by variants in the YWHAE gene (also known as 14-3-3ε) (Toyo-oka et al. 2003; Bi et al. Nat Genet 41:168-177, 2009). The YWHAE gene encodes the 14-3-3-epsilon protein, which binds and protects NUDEL, a phosphorylated protein important in regulating dynein activity in M phase. It has been predicted that 14-3-3-epsilon protein is required for NEDUL localization and cytoplasmic dynein function and might be important for neuronal migration (Toyo-oka et al. 2003). Submicroscopic deletions or duplication of 17p13.3 including PAFAH1B1 and YWHAE have been reported in MDLS patients (Chong et al. 1997; Toyo-oka et al. 2003; Bi et al. 2009). Of note, no point variants in the YWHAE gene have yet been reported in MDLS patients; therefore, aCGH analysis for deletions and duplications within the YWHAE gene should be performed first.

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity of this test is currently unknown.

Testing Strategy

This test provides full coverage of all coding exons of the YWHAE 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

Candidates for this test are patients with symptoms consistent with Miller-Dieker lissencephaly syndrome and family members of patients who have known YWHAE variants.


Official Gene Symbol OMIM ID
YWHAE 605066
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Miller-Dieker Lissencephaly Syndrome 247200


  • Barkovich, A. J., et.al. (1991). "The spectrum of lissencephaly: report of ten patients analyzed by magnetic resonance imaging." Ann Neurol 30(2): 139-46. PubMed ID: 1897907
  • Bi, W., et.al. (2009). "Increased LIS1 expression affects human and mouse brain development." Nat Genet 41(2): 168-77. PubMed ID: 19136950
  • Chong, S. S., et.al. (1997). "A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3." Hum Mol Genet 6(2): 147-55. PubMed ID: 9063734
  • Dobyns, W. B., et.al. (1991). "Clinical and molecular diagnosis of Miller-Dieker syndrome." Am J Hum Genet 48(3): 584-94. PubMed ID: 1671808
  • Schinzel, A. (1988). "Microdeletion syndromes, balanced translocations, and gene mapping." J Med Genet 25(7): 454-62. PubMed ID: 3050093
  • Toyo-oka, K., et.al. (2003). "14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome." Nat Genet 34(3): 274-85. PubMed ID: 12796778


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

loading Loading... ×


An error has occurred while calculating the price. Please try again or contact us for assistance.

View Ordering Instructions

1) Select Test Method (Platform)

1) Select Test Type

2) Select Additional Test Options

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
Copy Text to Clipboard