Walker-Warburg Syndrome via the RXYLT1/TMEM5 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
8807 RXYLT1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8807RXYLT181479 81479(x2) $890 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 backbone).

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

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

For Sanger Sequencing click here.

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.


Genetic Counselors


  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Walker-Warburg syndrome (WWS, OMIM 236670) is a genetically heterogeneous congenital muscular dystrophy in which many causative genes have been previously identified. These genes include POMT1, POMT2, POMGNT1, FKTN, FKRP, ISPD, and LARGE, each of which is believed to be involved in post translational modification of the sarcolemma-spanning protein alpha dystroglycan (ADG). Loss of function of any of these genes results in hypoglycosylation of ADG and reduced binding of ADG to the basal lamina through laminin (Barresi and Campbell. J Cell Sci 119:199-207, 2006). WWS is the most severe form of ADG-related congenital muscular dystrophy, presenting with profound hypotonia, defective neuronal migration and associated structural brain and eye abnormalities. CNS findings include cobblestone lissencephaly, cerebellar malformations, microophthalmia and cataracts. Patients have profound mental retardation and typically die in the first year of life. Muscle biopsies demonstrate a dystrophic process and markedly reduced or absent staining with antibodies to the glycolepitope of ADG. The genes referenced above account for only approximately half of all cases of WWS. A newly discovered gene, RXYLT1/TMEM5, has been shown to lead to severe cobblestone lissencephaly and a clinical presentation consistent with WWS (OMIM 615041; Vuillaumier-Barrot et al. Am J Hum Genet 91:1135-1143, 2012).


Mutations of the RXYLT1 gene are a documented cause of autosomal recessive severe cobblestone lissencephaly and other findings consistent with Walker-Warburg syndrome (Vuillaumier-Barrot et al. Am J Hum Genet 91:1135-1143, 2012). RXYLT1 (OMIM 605862) encodes a transmembrane protein that has a glycosyltransferase domain, although enzymatic activity has not yet been demonstrated. Mutations in RXYLT1 reported to date include small deletions and insertions and amino acid substitutions (http://www.LOVD.nl/TMEM5).

Clinical Sensitivity - Sequencing with CNV PGxome

Among fifty-eight families with severe cobblestone lissencephaly, Vuillaumier-Barrot et al. (Am J Hum Genet 91:1135-1143, 2012), found RXYLT1 mutations in five, or 9%. Among this same cohort, the relative frequency of genetically diagnosed cases is: POMT1 (42%), POMT2 (17%), POMGNT1 (17%), RXYLT1 (9%), ISPD (9%), LARGE (3%), and FKRP (3%). Sequence analysis of genomic DNA for RXYLT1 should have high analytical sensitivity because all RXYLT1 mutations identified to date are detectable by this method.

Testing Strategy

This test provides full coverage of all coding exons of the RXYLT1 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 severe cobblestone lissencephaly and other symptoms consistent with Walker-Warburg syndrome. Individuals with immunofluorescence results demonstrating hypoglycosylation of ADG in muscle. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RXYLT1.


Official Gene Symbol OMIM ID
RXYLT1 605862
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Barresi, R. andĀ Campbell, K. P. (2006). "Dystroglycan: from biosynthesis to pathogenesis of human disease." J Cell Sci 119(Pt 2): 199-207. PubMed ID: 16410545
  • Leiden Open Variation Database (TMEM5).
  • Vuillaumier-Barrot S. et al. (2012). "Identification of mutations in TMEM5 and ISPD as a cause of severe cobblestone lissencephaly." Am J Hum Genet 91: 1135-1143. PubMed ID: 23217329


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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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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