Wiskott-Aldrich Syndrome, X-linked Thrombocytopenia, and X-linked Congenital Neutropenia, via the WAS Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 9963 | WAS | 81406 | 81406,81479 | $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.
Clinical Features and Genetics
Clinical Features
Wiskott-Aldrich syndrome (WAS; OMIM 301000) and X-linked thrombocytopenia (XLT; OMIM 313900) are characterized by thrombocytopenia (platelet counts 5,000-50,000/μl) with markedly small-sized platelets. WAS is often detected in infancy through bleeding problems such as easy bruising, petechiae, and excessive bleeding during circumcision. Other features may include eczema, recurrent bacterial and viral infections, severe hemorrhaging, autoimmune disease such as hemolytic anemia or immune thrombocytopenic purpura, and lymphomas. Severity of WAS varies from lethal infantile forms to adult intermittent thrombocytopenia. X-linked congenital neutropenia (XLN; OMIM 300299) is characterized by absolute neutrophil counts (ANC) consistently below 500/μl and severe systemic bacterial infections that may begin in early infancy or during adolescence (Ancliff et al. Blood 108:2182-2189, 2006).
Genetics
WAS and related disorders exhibit X-linked recessive inheritance. Nearly all affected individuals are male. Female carriers are usually asymptomatic. The WAS gene (OMIM 300392) encodes a major regulator of actin polymerization in hematopoietic cells. Many causative variants in WAS have been reported. The causative variants are roughly 35% missense, 25% frameshift, 20% splicing, 15% nonsense, and 5% other. Although there are exceptions, patients carrying missense variants are generally less severely affected than those carrying nonsense, frameshift, or splicing variants (Jin et al. Blood 104:4010-4019, 2004; Imai et al. Blood 103:456-464, 2004; Lutskiy et al. J Immunol 175:1329-1336, 2005). In the outbred U.S. population, no variants are common. A fraction of patients are mosaic for blood cells with revertant WAS genes (Ariga et al. J Immunol 166:5245-5249, 2001; Wada et al. PNAS 98:8697-8702, 2001). Three variants in exon 9 (i.e. p.Leu270Pro, p.Ser272Pro, and p.Ile294Thr) have been shown to result in constitutively active WAS protein, which is known to cause X-linked neutropenia (XLN) with normal platelet counts (Devriendt et al. Nature 27:313-317, 2001; Ancliff et al. Blood 108:2182-2189, 2006).
Clinical Sensitivity - Sequencing with CNV PGxome
Approximately 95% of causative WAS variants are detectable by DNA sequencing (Imai et al. 2004; Lutskiy et al. 2005). If the diagnosis of WAS is distinguished from other severe immunodeficiency disorders and also from immune thrombocytopenic purpura, the overall sensitivity of this test will be high (Filipovich et al. 2007).
Testing Strategy
This test provides full coverage of all coding exons of the WAS 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
All male patients with symptoms of WAS or related disorders and with a family history of X-linked inheritance are candidates for this test. Female patients should only be considered if they have affected fathers or if they have a strong family history (Lutskiy et al. Blood 100:2763-2768, 2002). Males with congenital neutropenia and evidence of X-linked familial inheritance are also candidates.
All male patients with symptoms of WAS or related disorders and with a family history of X-linked inheritance are candidates for this test. Female patients should only be considered if they have affected fathers or if they have a strong family history (Lutskiy et al. Blood 100:2763-2768, 2002). Males with congenital neutropenia and evidence of X-linked familial inheritance are also candidates.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| WAS | 300392 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Severe Congenital Neutropenia X-Linked | 300299 | |
| Thrombocytopenia, X-Linked | 313900 | |
| Wiskott-Aldrich Syndrome | 301000 |
Related Tests
| Name |
|---|
| Autoimmune Lymphoproliferative Syndrome via the FAS Gene |
| Common Variable Immune Deficiency/IgA Deficiency via the TNFRSF13B Gene |
| Severe Congenital Neutropenia and Neutrophilia via the CSF3R Gene |
Citations
- Alexandra H Filipovich, et.al. (2007). "WAS-Related Disorders."
- Alexandra H Filipovich, et.al. (2007). "WAS-Related Disorders."
- Ancliff PJ, Blundell MP, Cory GO, Calle Y, Worth A, Kempski H, Burns S, Jones GE, Sinclair J, Kinnon C, Hann IM, Gale RE, Linch DC, Thrasher AJ. 2006. Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia. Blood 108: 2182–2189. PubMed ID: 16804117
- Ancliff PJ, Blundell MP, Cory GO, Calle Y, Worth A, Kempski H, Burns S, Jones GE, Sinclair J, Kinnon C, Hann IM, Gale RE, Linch DC, Thrasher AJ. 2006. Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia. Blood 108: 2182–2189. PubMed ID: 16804117
- Ariga, T., et.al. (2001). "Spontaneous in vivo reversion of an inherited mutation in the Wiskott-Aldrich syndrome." J Immunol 166(8): 5245-9. PubMed ID: 11290809
- Devriendt, K., et.al. (2001). "Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia." Nat Genet 27(3): 313-7. PubMed ID: 11242115
- Imai, K., et.al. (2004). "Clinical course of patients with WASP gene mutations." Blood 103(2): 456-64. PubMed ID: 12969986
- Imai, K., et.al. (2004). "Clinical course of patients with WASP gene mutations." Blood 103(2): 456-64. PubMed ID: 12969986
- Jin, Y., et.al. (2004). "Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation." Blood 104(13): 4010-9. PubMed ID: 15284122
- Lutskiy, M. I., et.al. (2002). "Wiskott-Aldrich syndrome in a female." Blood 100(8): 2763-8. PubMed ID: 12351383
- Lutskiy, M. I., et.al. (2002). "Wiskott-Aldrich syndrome in a female." Blood 100(8): 2763-8. PubMed ID: 12351383
- Lutskiy, M. I., et.al. (2005). "Genotype-proteotype linkage in the Wiskott-Aldrich syndrome." J Immunol 175(2): 1329-36. PubMed ID: 16002738
- Wada, T., et.al. (2001). "Somatic mosaicism in Wiskott--Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism." Proc Natl Acad Sci U S A 98(15): 8697-702. PubMed ID: 11447283
- WASbase: Mutation registry for Wiskott-Aldrich syndrome (WAS)
- WASPbase
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
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
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ORDER OPTIONS
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