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Test Code GNHTC Hereditary Thrombocytopenia Gene Panel, Next-Generation Sequencing, Varies


Ordering Guidance


This test is designed to evaluate a variety of hereditary thrombocytopenia disorders and to be utilized for genetic confirmation of a phenotypic diagnosis of a thrombocytopenia disorder.

 

If testing for hereditary platelet disorders using a larger, comprehensive panel is desired, a 70-gene platelet panel is available; order GNPLT / Platelet Disorders, Comprehensive Gene Panel, Next-Generation Sequencing, Varies.

 

This test is not designed to evaluate for hereditary bleeding disorders. For patients with clinical suspicion of an inherited bleeding disorder, it is important to exclude plasmatic factor deficiencies eg, von Willebrand disease, hemophilia, or other factor deficiencies, prior to considering an inherited platelet function defect. If bleeding is the indication for testing and testing for hereditary bleeding disorders is desired, bleeding panels are available. For more information see GNBLF / Bleeding Disorders, Focused Gene Panel, Next-Generation Sequencing, Varies or GNBLC / Bleeding Disorders, Comprehensive Gene Panel, Next-Generation Sequencing, Varies.

 

For assessment of hereditary platelet disorders that have ultrastructural abnormalities, such as gray platelet syndrome, order PTEM / Platelet Transmission Electron Microscopic Study, Whole Blood.

 

For assessment of hereditary platelet disorders due to quantitative surface glycoprotein deficiencies, order PLAFL / Platelet Glycoprotein Flow Platelet Surface Glycoprotein by Flow Cytometry, Blood.

 

Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

 

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Necessary Information


Platelet Esoteric Testing Patient Information is required. Testing may proceed without the patient information; however, the information aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to fill out the form and send with the specimen.



Specimen Required


Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.


Forms

1. Platelet Esoteric Testing Patient Information is required.

2. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

3. If not ordering electronically, complete, print, and send an Coagulation Test Request (T753) with the specimen.

Secondary ID

619341

Useful For

Evaluating hereditary thrombocytopenia disorders in patients with a personal or family history suggestive of a hereditary thrombocytopenia disorder

 

Diagnosing hereditary thrombocytopenia disorders for patients in whom phenotypic testing is nondiagnostic but there is a strong clinical suspicion of the hereditary thrombocytopenia disorder

 

Confirming a hereditary thrombocytopenia disorder diagnosis with the identification of a known or suspected disease-causing alteration in one or more of 36 genes associated with a variety of hereditary thrombocytopenia disorders

 

Determining the disease-causing alterations within one or more of these 36 genes to delineate the underlying molecular defect in a patient with a laboratory diagnosis of a thrombocytopenia disorder

 

Identifying the causative alteration for genetic counseling purposes

 

Prognosis and risk assessment based on the genotype-phenotype correlations

 

Providing a prognosis in syndromic hereditary thrombocytopenia disorders

 

Carrier testing for close family members of an individual with a hereditary thrombocytopenia disorder diagnosis

 

This test is not intended for prenatal diagnosis.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

The clinical workup for detecting inherited platelet disorders should begin with a careful review of complete blood cell count and peripheral blood smear results, as well as other platelet tests, such as light transmission platelet aggregometry, electrical impedance whole blood aggregometry, platelet function analyzer 100, platelet transmission electron microscopy (TEM), and platelet flow cytometric analysis. TEM is an essential tool for laboratory diagnosis of various hereditary platelet disorders that have ultrastructural abnormalities, such as gray platelet syndrome. Flow cytometry is the preferred method to assess hereditary platelet disorders due to quantitative surface glycoprotein deficiencies.

 

Platelet laboratory testing may not be able to identify all inherited platelet disorders. Occasionally, the clinical picture may be consistent with a defect in primary hemostasis, but the results of platelet function tests may be normal or nondiagnostic.

 

Genetic testing for hereditary platelet disorders is indicated if:

-Platelet tests indicate a deficiency or functional abnormality

-There is a clinical suspicion for a hereditary platelet disorder due to family history or patient’s clinical presentation

-Acquired causes of deficiencies associated with platelet disorders have been excluded

 

If a platelet disorder is a concern, a set of clinical guidelines from the British Society for Haematology on testing for heritable platelet disorders is freely available.(1)

 

For skin biopsy or cultured fibroblast specimens:

For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

Thrombocytopenia Gene Panel, NGS

Specimen Type

Varies

Specimen Minimum Volume

Blood: 1 mL; Cultured fibroblasts/skin biopsy: see Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Platelets have essential roles in primary hemostasis. Patients with either hereditary or acquired platelet disorders usually have bleeding diathesis, which can potentially be life-threatening. They may also have issues with the development and/or functioning of major organs.(2) Inherited platelet disorders can be syndromic (ie, associated with current or future development of other organ system defects) or non-syndromic (ie, isolated to thrombocytopenia with no other organ system defects).

 

A reliable laboratory diagnosis of a platelet disorder can significantly impact patients' and, potentially, their family members' clinical management and outcome. Identification of an alteration that is known or suspected to cause disease aids in confirmation of the diagnosis and potentially provides prognostic information, especially in syndromic inherited platelet disorders.

 

This panel evaluates 36 genes associated with a variety of hereditary thrombocytopenia disorders, including macrothrombocytopenia; sitosterolemia with macrothrombocytopenia; Baraitser-Winter syndrome 1 with macrothrombocytopenia; autosomal dominant thrombocytopenia 2; Scott syndrome; platelet abnormalities with eosinophilia and immune-mediated inflammatory disease; Takenouchi-Kosaki syndrome with thrombocytopenia; autosomal dominant thrombocytopenia 4; macrothrombocytopenia and sensorineural hearing loss; thrombocytopenia and susceptibility to cancer; Paris-Trousseau-Jacobson syndrome; syndrome with macrothrombocytopenia; thrombocytopenia 3; X-linked thrombocytopenia with dyserythropoiesis; GATA2 deficiency; myopathy associated with thrombocytopenia; amegakaryocytic thrombocytopenia with radioulnar synostoses 1 and 2; thrombocytopenia and erythrokeraderma; autosomal thrombocytopenia with normal platelets; thrombocytopenia anemia and myelofibrosis; congenital amegakaryocytic thrombocytopenia; May-Hegglin disorder/anomaly; Sebastian syndrome; MYH9-related disorders; autosomal dominant tubular aggregate myopathy-2; Quebec platelet disorder; platelet-type bleeding disorder 19; thrombocytopenia-absent radius (TAR) syndrome; familial platelet disorder with predisposition to acute myeloid leukemia; platelet-type bleeding disorder 20; Stormorken syndrome; York platelet syndrome; thrombocytopenia progressing to trilineage bone marrow failure; and Wiskott-Aldrich syndrome.

 

The risk for developing bleeding or other phenotypic features associated with these disorders and syndromes varies. Several of the genes on this panel have established bleeding, thrombocytopenia, or other hematologic or non-hematologic disease associations. Several of the genes on this panel also have expert group guidelines.(1,3-5)

 

It is recommended that genetic testing be offered to all patients suspected of having a heritable platelet disorder since some patients may have normal platelet laboratory testing results.(1,6)

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(7) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp, and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Comprehensive Hereditary Thrombocytopenia Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)

 

Reference transcript numbers may be updated due to transcript re-versioning. Always refer to the final patient report for gene transcript information referenced at the time of testing. Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

 

Genes analyzed:

ABCG5, ABCG8, ACTB, ACTN1, ANKRD26, ANO6, ARPC1B, CDC42, CYCS, DIAPH1, ETV6, FLI1, FLNA, FYB1, GATA1, GATA2, GNE, HOXA11, IKZF5, KDSR, MASTL, MECOM, MPIG6B, MPL, MYH9, ORAI1, PLAU, PRKACG, RBM8A, RUNX1, SLFN14, STIM1, THPO, TPM4, TUBB1, and WAS

Day(s) Performed

Varies

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81443

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GNHTC Thrombocytopenia Gene Panel, NGS 99970-6

 

Result ID Test Result Name Result LOINC Value
619342 Test Description 62364-5
619343 Specimen 31208-2
619344 Source 31208-2
619345 Result Summary 50397-9
619346 Result 82939-0
619347 Interpretation 59465-5
619348 Additional Results 82939-0
619349 Resources 99622-3
619350 Additional Information 48767-8
619351 Method 85069-3
619352 Genes Analyzed 82939-0
619353 Disclaimer 62364-5
619354 Released By 18771-6