Thrombocytopenia Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10307 ADAMTS13 81479,81479 Order Options and Pricing
ANKRD26 81479,81479
CYCS 81479,81479
GATA1 81479,81479
GP1BA 81479,81479
GP1BB 81404,81479
GP9 81479,81479
MASTL 81479,81479
MPL 81479,81479
MYH9 81479,81479
RUNX1 81479,81479
WAS 81406,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10307Genes x (12)81479 81404, 81406, 81479 $930 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Thrombocytopenia is a blood disorder characterized by low platelet counts. In adults, low platelet numbers are typically considered below 150,000/microL. Bleeding manifestations of thrombocytopenia include primarily excessive bruising (purpura), petechiae, prolonged bleeding from cuts or from surgical procedures, spontaneous nose bleeds, and in women, heavy menstrual flows. Thrombocytopenia and consequent bleeding diatheses range in severity from mild to severe. About half of the inherited thrombocytopenias are syndromic disorders with additional defects including physical and neurological anomalies, and immunodeficiencies (Balduini et al. 2013). Some inherited thrombocytopenias are associated with an increased risk of developing myelodysplastic syndrome (MDS) and acute leukemia (AL) (Churpek et al. 2013). It is important to distinguish inherited thrombocytopenias from immune / idiopathic thrombocytopenias (ITP) in order to inform clinical management and identify potential at risk family members.

Genetics

This panel test is designed to detect variants in several genes associated with either autosomal dominant, autosomal recessive, or X-linked forms of inherited thrombocytopenias. The genes included in this panel have been associated with both syndromic and non-syndromic forms of inherited thrombocytopenia and represent some of the more common forms of inherited thrombocytopenia reported in the literature. Thrombocytopenias are typically divided into three distinct groups based upon platelet size: large / macrothrombocytopenias, small / microthrombocytopenias, and thrombocytopenias with normal sized platelets.

Macrothrombocytopenias

MYH9--May-Hegglin Anomaly, Sebastian Syndrome, Fechtner Syndrome, and Epstein Syndrome. Inheritance is autosomal dominant. Clinical features may include high tone deafness, cataracts, leukocyte inclusions, and kidney disease leading in some cases to renal failure. Variants affecting the head domain of the Myosin-IIA protein are associated with a higher risk of nephropathy and deafness than variants affecting the tail domain (Pecci et al. 2014).

GP1BA, GP1BB, GP9--Bernard Soulier Syndrome and Platelet Type von Willebrand Disease (PT-VWD, GP1BA), and Giant Platelet Syndrome. Inheritance is autosomal recessive. Variants in GP1BA associated with PT-VWD are inherited in an autosomal dominant manner.

GATA1--X-linked thrombocytopenia. Inheritance is X-linked recessive. Clinical features include erythrocytic anemia, globin gene transcription defects, and porphyria.

Microthrombocytopenias WAS--Wiskott-Aldrich syndrome, X-linked thrombocytopenia. Inheritance is X-linked recessive. Clinical features may include eczema, recurrent bacterial and viral infections, severe hemorrhaging, autoimmune disease such as hemolytic anemia or immune thrombocytopenic purpura, lymphomas, and X-linked Congenital Neutropenia.

Thrombocytopenias with Normal Platelet Size

CYCS--Cytochrome-C gene related thrombocytopenia. Inheritance is autosomal dominant.

ANKRD26, MASTL--Thrombocytopenia 2 (THC2) is characterized by moderately low platelet counts (family averages = 40-60/nl) (Savoia et al. 1999; Drachman et al. 2000). Platelets are of normal size. Patients often bruise easily and have moderate bleeding problems. Thrombopoietin levels are mildly elevated. Variants in ANKRD26 are associated with predisposition to Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML); up to a 30 fold increase in the frequency of MDS and AML has been reported in patients with ANKRD26 gene variants (Noris et al. 2011; Noris et al. 2013; Marquez et al. 2014).

RUNX1--Familial Thrombocytopenia with Predisposition to Acute Myeloid Leukemia (AML). Inheritance is autosomal dominant. Over 40% of patients with germline variants in the RUNX1 gene develop MDS / AML at a mean age of ~ 33 years (Reviewed in Churpek et al. 2013).

MPL--Congenital Amegakaryocytic Thrombocytopenia (CAMT). Inheritance is autosomal recessive and variants in MPL have been identified in ~ 60% of patients. Clinical features include absent or reduced megakaryocytes and development of aplastic anemia and pancytopenia. AML has been reported in some patients (Ballmaier and Gerheshausen 2009).

ADAMTS13--Thrombotic Thrombocytopenic Purpura (TTP), often described as Upshaw-Schulman syndrome (USS), is a rare blood condition characterized by frequent relapses of fever, platelet thrombi in microvasculature, hemolytic anemia, consumptive thrombocytopenia, neurologic symptoms, renal disease, and possible organ failure (Levy et al. 2001). Inheritance is autosomal recessive.

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

Testing Strategy

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).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is designed to identify variants in some of the more common genes associated with thrombocytopenias. While the overall clinical sensitivity of this panel is difficult to determine, in a recent study of 272 patients with macrothrombocytopenia, ~48% of patients harbored pathogenic variants in either the MYH9 gene (~ 38%), the Bernard Soulier genes (~ 10%), or the GATA1 gene (< 1%) (Kunishima, S. Thrombocytopenia, ISTH Webinar 2015: WEB150325). In general, ~ 50% of inherited thrombocytopenias are the result of disorders that are not yet characterized (Balduini et al. 2013).

The majority of variants reported in the thrombocytopenia genes in this panel are missense and nonsense variants. Large deletions account for ~24% of the reported RUNX1 gene variants, but in general, large, multi-exon and whole gene deletions are rare among the thrombocytopenia panel genes. In addition to the RUNX1 gene, large deletions have also been reported in the GP1BB, MYH9, and WAS genes (Human Gene Mutation Database).

Indications for Test

Patients with a family history of thrombocytopenia who may or may not have other defects including immunodeficiencies, and physical or neurological anomalies. Patients with a family history of MDS / AML. The thrombocytopenia panel may also be helpful for patients with no family history of thrombocytopenia, but who develop thrombocytopenia over time in order to help rule out a diagnosis of an inherited thrombocytopenia.

Genes

Official Gene Symbol OMIM ID
ADAMTS13 604134
ANKRD26 610855
CYCS 123970
GATA1 305371
GP1BA 606672
GP1BB 138720
GP9 173515
MASTL 608221
MPL 159530
MYH9 160775
RUNX1 151385
WAS 300392
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Balduini et al. 2013. PubMed ID: 23397552
  • Ballmaier M., Germeshausen M. 2009. British journal of haematology. 146: 3-16. PubMed ID: 19388932
  • Churpek et al. 2013. PubMed ID: 22691122
  • Drachman JG. et al. 2000. Blood. 96: 118-25. PubMed ID: 10891439
  • Human Gene Mutation Database (Bio-base).
  • Levy GG. et al. 2001. Nature. 413: 488-94. PubMed ID: 11586351
  • Marquez R. et al. 2014. Leukemia & lymphoma. 55: 2945-6. PubMed ID: 24628296
  • Noris P. et al. 2011. Blood. 117: 6673-80. PubMed ID: 21467542
  • Noris P. et al. 2013. Blood. 122: 1987-9. PubMed ID: 24030261
  • Pecci A. et al. 2010. European journal of haematology. 84: 291-7. PubMed ID: 20002731
  • Pecci A. et al. 2014. Human mutation. 35: 236-47. PubMed ID: 24186861
  • Pippucci T. et al. 2011. American journal of human genetics. 88: 115-20. PubMed ID: 21211618
  • Savoia A. et al. 1999. American journal of human genetics. 65: 1401-5. PubMed ID: 10521306

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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