Walker-Warburg Syndrome via the CRPPA/ISPD Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7337 CRPPA 81405 81405,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7337CRPPA81405 81405(x1), 81479(x1) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Walker-Warburg syndrome (WWS, OMIM 236670) is a genetically heterogeneous congenital muscular dystrophy for which six causative genes have been previously identified. These genes are POMT1, POMT2, POMGNT1, FKTN, FKRP, 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 the six 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 six genes referenced above account for only approximately half of all cases of WWS. A newly discovered gene, CRPPA/ISPD, has been shown to lead to ADG hypoglycoslyation and a clinical presentation of WWS (Willer et al. Nat Genet 44:575-580, 2012 and Roscioli et al. Nat Genet 44:581-587, 2012).

Genetics

Loss of function variants in the CRPPA gene are the seventh documented cause of Walker-Warburg syndrome (Willer et al. 2012 and Roscioli et al. 2012). CRPPA encodes a protein that may be involved in lipid precursor synthesis (Willer et al. 2012), thus representing a novel pathophysiological mechanism for ADG hypoglycosylation and WWS. CRPPA-related WWS is inherited in an autosomal recessive manner. CRPPA variants reported thus far include splice site variants, nonsense variants, a small deletion, gross deletions, and a variant that extends the amino acid reference sequence.

The isoprenoid synthase domain containing gene is encoded by exons 1- 10 of the CRPPA gene located on chromosome 7p21.2.

Clinical Sensitivity - Sequencing with CNV PG-Select

In a cohort of 11 WWS cases in which variants in POMT1, POMT2, POMGNT1, FKTN, FKRP, and LARGE had been ruled-out, Willer et al. (2012) found 7 patients (6 unrelated cases) with loss of function CRPPA gene variants. Based on this finding, CRPPA may be the most common cause of WWS. The occurrence of CRPPA variants in other forms of dystroglycanopathy is unknown at present (Willer et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the CRPPA gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with 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 CRPPA.

Gene

Official Gene Symbol OMIM ID
CRPPA 614631
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Barresi, R. and Campbell, K. P. (2006). "Dystroglycan: from biosynthesis to pathogenesis of human disease." J Cell Sci 119(Pt 2): 199-207. PubMed ID: 16410545
  • Roscioli, T., et.al. (2005). "Pallister-Hall syndrome: unreported skeletal features of a GLI3 mutation." Am J Med Genet A 136A(4): 390-4. PubMed ID: 16007608
  • Willer T, Lee H, Lommel M, Yoshida-Moriguchi T, Bernabe DBV de, Venzke D, Cirak S, Schachter H, Vajsar J, Voit T, Muntoni F, Loder AS, et al. 2012. ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome. Nature Genetics 44: 575–580. PubMed ID: 22522420

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

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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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