Invitae WAS-Related Disorders Test

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  • Test code: 05318
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Test description

WAS-related disorders include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN). These are a spectrum of hematopoietic disorders that primarily affect platelets and lymphocytes and whose symptoms range from mild to severe. These conditions are all due to pathogenic variants in the WAS gene, located on the X chromosome.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.

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Primary panel (1 gene)

WAS

Alternative tests to consider

These genes can also be ordered as part of a broader panel. Depending on the individual’s clinical and family history, this panel may be appropriate and can be ordered at no additional charge.

  • WAS-related disorders
    • Wiskott-Aldrich syndrome
    • X-linked thrombocytopenia (XLT)
    • X-linked severe congenital neutropenia

WAS-related disorders include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN). These are a spectrum of hematopoietic disorders that primarily affect platelets and lymphocytes and whose symptoms range from mild to severe. These conditions are all due to pathogenic variants in the WAS gene, located on the X chromosome.

The WAS-spectrum of disorders typically presents in infancy. Males develop thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, intermittent or chronic petechiae, thrombocytopenia purpura, eczema, and recurrent infections resulting in significant morbidity and mortality. Those who survive these early symptoms may later develop various autoimmune disorders, including hemolytic anemia, immune thrombocytopenia purpura (ITP), immune-mediated neutropenia, arthritis, and vasculitis, among others.

Males with Wiskott-Aldrich syndrome have any combination of a triad of symptoms, including: 1) bloody diarrhea, mucosal bleeding, or petechiae, 2) eczema, and 3) recurrent middle-ear infections and purulent drainage. There is an increased risk of lymphomas—particularly B-cell lymphomas—among those exposed to the Epstein-Barr virus.

X-linked congenital neutropenia causes congenital neutropenia associated with myelodysplasia, increased myeloid cell apoptosis, and lymphoid cell abnormalities. Affected individuals have an increased risk of developing myelodysplastic syndrome and acute myelogenous leukemia.

Males with X-linked thrombocytopenia have small platelet volume and intermittent thrombocytopenia. While life-expectancy is not typically diminished, severe disease-related symptoms such as severe infections, bleeding, autoimmune diseases, and malignancies may cause significant morbidity.

Female carriers of a WAS pathogenic variant rarely have significant clinical symptoms and generally have no immunologic or biochemical markers of the disorder; however, some may have mild thrombocytopenia. Rarely, females may have symptoms of Wiskott-Aldrich syndrome due to skewed X-inactivation.

WAS is the only known gene associated with WAS-related disorders. Analysis of the WAS gene detects a pathogenic variant in nearly 100% of both affected males and unaffected carrier females.

WAS-related disorders are inherited in an X-linked recessive pattern.

These disorders are fully penetrant in males with a pathogenic WAS variant.

Prevalence is estimated at 1 in 100,000 to 1 in 1,000,000 individuals for all WAS-related disorders.

Analysis of the WAS gene may be considered for individuals with a personal and/or family history of:

  • profound thrombocytopenia (<70,000 platelets/mm2) and small platelet size
  • recurrent bacterial or viral infections
  • persistent neutropenia
  • eczema
  • lymphoma
  • autoimmune disease
  • absent or decreased Wiskott-Aldrich syndrome protein (WASP), as determined by flow cytometry or western blotting
  • arrested development of the bone marrow in the absence of other clinical findings of Wiskott-Aldrich syndrome (WASP expression is normal in individuals with XLN)

Clinical diagnostic criteria for Wiskott-Aldrich syndrome have been established by the European Society for Immunodeficiencies.

If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type that is not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle, but deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Sample requirements page for more details.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
WAS NM_000377.2