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Glanzmann's Thrombasthenia via the ITGB3 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
11403 ITGB3 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11403ITGB381479 81479,81479 $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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

Glanzmann's Thrombasthenia (GT) is the most commonly inherited disorder of platelet function. Extensive phenotypic variability is seen with GT where mucocutaneous bleeding episodes are the most uniform symptom. Other clinical features may include hemorrhage, easy bruising, postpartum bleeding, and menorrhagia. Platelet count and morphology are typically normal in patients with GT making diagnosis more difficult (Nurden et al. 2013). Bleeding in patients affected with GT is due to loss of the integrin receptor complex CD41, also known as GpIIb/IIIa, thereby preventing platelet binding to fibrinogen at sites of vessel injury. Onset age is directly correlated to the amount of functional CD41 integrin complex with severe cases displaying symptoms in early childhood. Platelet infusions and recombinant factor VIIa treatments have been shown to curtail symptoms (Coppola et al. 2004; Poon et al, 2004). Genetic testing is helpful for differential diagnosis of GT from other disorders displaying mucocutaneous bleeding and platelet function defects.

Genetics

GT is inherited in an autosomal recessive manner through mutations in either the ITGB3 or ITGA2B genes. Mutations in ITGB3 are detected in slightly under half of patients with GT. To date, nearly 100 mutations have been described throughout the ITGB3 gene in patients with GT with missense and small deletions being most common. Missense mutations primarily disrupt αIIbβ3 integrin complex formation where small deletions typically lead to formation of a premature stop codon (Jallu et al. 2010; http://med.mssm.edu/glanzmanndb). Frequently observed mutations include c.1053_1058del in North Africans and c.2031-2041del in Iraqi-Jewish ethnicities (Fiore et al. 2012). Large deletions of the ITGB3 gene are rarely found in GT patients (Jallu et al. 2010). ITGB3 protein is the beta subunit making up the αIIbβ3 integrin complex, also known as CD41 and GpIIb/IIIa. Activation of the αIIbβ3 integrin complex allows platelets to bind fibrinogen and join to form platelet plugs at sites of vessel injury (Nurden et al, 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

Mutations in either ITGB3 or ITGA2B account for nearly all cases of GT. Clinical sensitivity for patients with GT symptoms (absence of platelet aggregation and αIIbβ3 expression) is >95% (Fiore et al. 2012). Analytical sensitivity for detection of causative mutations in both genes is >95% (Fiore et al. 2012) .

Testing Strategy

This test provides full coverage of all coding exons of the ITGB3 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

Patients with excessive bleeding due to platelet function disorder are recommended for testing. Ideal candidates have decreased αIIbβ3 expression indicative of GT (Fiore et al. 2012). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ITGB3.

Gene

Official Gene Symbol OMIM ID
ITGB3 173470
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Glanzmann's Thrombasthenia AR 273800

Citations

  • Coppola A. et al. 2004. Thrombosis and haemostasis. 92: 1450-2. PubMed ID: 15583755
  • Fiore M. et al. 2012. European journal of human genetics : EJHG. 20: N/A. PubMed ID: 22781097
  • Jallu V, Dusseaux M, Panzer S, Torchet M-F, Hezard N, Goudemand J, Brevern AG de, Kaplan C. 2010. AlphaIIbbeta3 integrin: new allelic variants in Glanzmann thrombasthenia, effects on ITGA2B and ITGB3 mRNA splicing, expression, and structure-function. Hum. Mutat. 31: 237-246. PubMed ID: 20020534
  • Nurden AT, Fiore M, Nurden P, Pillois X. 2011. Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models. Blood 118: 5996-6005. PubMed ID: 21917754
  • Nurden AT. et al. 2013. Seminars in thrombosis and hemostasis. 39: 642-55. PubMed ID: 23929305
  • Poon MC. et al. 2004. Journal of thrombosis and haemostasis : JTH. 2: 1096-103. PubMed ID: 15219192

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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View Ordering Instructions

1) Select Test Method (Platform)


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.
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