Miller-Dieker Lissencephaly Syndrome via the YWHAE Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT
8893 YWHAE$890 8147981479,81479 Add to Order

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.

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

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average


Genetic Counselors


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 "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 LIS1-associated lissencephaly patients (OMIM 607432), explained by two additional genes deletion, CRK and YWHAE (also known as 14-3-3ε), on 17p13.3 distal to LIS1 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 LIS1-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 mutations 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 LIS1 and/or YWHAE have been reported in MDLS patients (Chong et al. 1997; Toyo-oka et al. 2003; Bi et al. 2009). Of note, no point mutations 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.

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.

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

Clinical Sensitivity - Sequencing with CNV

Sensitivity of this test is currently unknown.

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 mutations.


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., (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., (2009). "Increased LIS1 expression affects human and mouse brain development." Nat Genet 41(2): 168-77. PubMed ID: 19136950
  • Chong, S. S., (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., (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., (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

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

Specimen Types

Specimen Requirements and Shipping Details

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