Warburg Micro Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10185 RAB18 81479,81479 Order Options and Pricing
RAB3GAP1 81479,81479
RAB3GAP2 81479,81479
TBC1D20 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10185Genes x (4)81479 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Warburg Micro syndrome (WMS) is a rare autosomal recessive disorder with brain, eye, and endocrine abnormalities. WMS is characterized by congenital microcephaly, cortical dysplasia, agenesis or hypoplasia of the corpus callosum, microphthalmia, microcornea, congenital cataracts, optic atrophy, profound intellectual disability, and hypogenitalism (Derbent et al. 2004; Graham et al. 2004; Handley et al. 2013).

WMS may be distinguished from other similar clinical disorders such as Cerebro-Oculo-Facio-Skeletal syndrome and Cockayne syndrome by normal nucleotide excision repair (NER) in cultured fibroblasts. It is also distinguished by the presence of significant visual abnormalities, frontal polymicrogyria, thin corpus callosum, and cortical atrophy by MRI. The most difficult differential diagnosis would be between WMS and Martsolf syndrome (MS). MS syndrome patients have a higher life expectancy, and MS is considered milder than WMS (Morris-Rosendahl et al. 2010).

WMS is a heterogeneous disorder; however, the gene involved cannot be ascertained based on clinical phenotype (Handley et al. 2013; Liegel et al. 2013).

Genetics

WMS is an autosomal recessive disorder associated with causative variants in four genes: RAB3GAP1, RAB3GAP2, RAB18 and TBC1D20. MS has been associated with pathogenic variants in RAB3GAP2. Together, pathogenic variants in these genes account for about 50% of WMS and MS cases. Rabs are small G proteins of the Ras superfamily, which are involved in vesicular trafficking. RAB3GAP, which regulates Rab3 activity, is a heterodimeric complex consisting of a catalytic subunit encoded by RAB3GAP1 and a noncatalytic subunit encoded by RAB3GAP2. RAB18 encoded protein is mostly localized to lipid droplets and has a role in lipid dynamics and lipid storage activities. However, its relationship to RAB3GAP1 and RAB3GAP2 has not been investigated (Martin et al. 2005; Handley et al. 2013). Recently, TBC1D20, which is a RabGTPase-activating protein, has shown to be associated with WMS (Liegel et al. 2013).

So far ~50 pathogenic variants in RAB3GAP1 (truncating mutations, missense, splicing, small and gross deletions); ~10 pathogenic variants in RAB3GAP2 (truncating mutations, missense, splicing, small deletions and insertions), ~5 pathogenic variants in RAB18 (missense, nonsense, small and gross deletions) and ~5 pathogenic variants in TBC1D20 (nonsense, small and gross deletions) have been reported that are associated with WMS and MS (Human Gene Mutation Database).

See individual gene test descriptions for more information on molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

In a study that investigated 153 families (144 WMS and 9 MS patients), pathogenic variants were identified in RAB3GAP1 (41% of cases), RAB3GAP2 (7% of cases), and RAB18 (5% of cases) (Handley et al. 2013). Sequence analysis of 77 families affected by WMS (negative for RAB3GAP1, RAB3GAP2, and RAB18 pathogenic variants), found seven individuals found to be homozygous for TBC1D20 pathogenic variants (Liegel et al. 2013).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 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).

Indications for Test

All patients with symptoms suggestive of Warburg Micro syndrome and Martsolf syndrome are candidates.

Genes

Official Gene Symbol OMIM ID
RAB18 602207
RAB3GAP1 602536
RAB3GAP2 609275
TBC1D20 611663
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Derbent M. et al. 2004.  American Journal of Medical Genetics. Part A 128A: 232–4. PubMed ID: 15216542
  • Graham JM. et al. 2004. American Journal of Medical Genetics. Part A 128A: 235–45. PubMed ID: 15216543
  • Handley MT. et al. 2013. Human Mutation 34: 686–96. PubMed ID: 23420520
  • Human Gene Mutation Database (Bio-base).
  • Liegel RP. et al. 2013. American Journal of Human Genetics. 93: 1001-14. PubMed ID: 24239381
  • Martin S. et al. 2005. The Journal of Biological Chemistry. 280: 42325-35. PubMed ID: 16207721
  • Morris-Rosendahl DJ. et al. 2010. European Journal of Human Genetics : Ejhg. 18: 1100-6. PubMed ID: 20512159

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.

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 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.

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