Test Code GNSPD Platelet Storage Pool Deficiency Gene Panel, Next-Generation Sequencing, Varies

Ordering Guidance

This test is designed to evaluate a variety of hereditary platelet storage pool deficiencies and to be utilized for genetic confirmation of a phenotypic diagnosis of a platelet storage pool deficiency. 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 variants 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

Specimen Type: Whole blood

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.

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) 4 days/Refrigerated

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

619327

Useful For

Evaluating hereditary platelet storage pool deficiencies in patients with a personal or family history suggestive of a hereditary platelet storage pool deficiency

Diagnosing hereditary platelet storage pool deficiencies for patients in whom phenotypic testing is nondiagnostic, but there is a strong clinical suspicion of the hereditary platelet storage pool deficiency

Confirming a hereditary platelet storage pool deficiency diagnosis with the identification of a known or suspected disease-causing alteration in one or more of 24 genes associated with a variety of hereditary platelet storage pool deficiencies

Determining the disease-causing alterations within one or more of these 24 genes to delineate the underlying molecular defect in a patient with a laboratory diagnosis of a platelet storage pool deficiency

Identifying the causative alteration for genetic counseling purposes

Prognosis and risk assessment based on the genotype-phenotype correlations

Providing a prognosis in syndromic hereditary platelet storage pool deficiencies

Carrier testing for close family members of an individual with a hereditary platelet storage pool deficiency diagnosis

This test is not intended for prenatal diagnosis

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 (PFA-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 non-diagnostic.

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 patientâ€™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.

Special Instructions

Method Name

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

Reporting Name

Storage Pool Deficiency Panel, NGS

Specimen Type

Varies

Specimen Minimum Volume

1 mL

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 nonsyndromic (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 24 genes associated with a variety of hereditary platelet storage pool deficiencies, including reduced adenosine diphosphate (ADP)-induced platelet aggregation; Hermansky-Pudlak syndrome; Paris-Trousseau-Jacobsen syndrome; platelet-type bleeding disorder 17; Chediak-Higashi syndrome; autism with platelet dense granule defect; gray platelet syndrome; autosomal dominant tubular aggregate myopathy-2; Quebec platelet disorder; Stormorken syndrome; York platelet syndrome; familial hemophagocytic lymphohistiocytosis type 5; ARC syndromes (arthrogryposis, renal dysfunction, and cholestasis) 1 and 2; 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 nonhematologic 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 deletion-insertions 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 Platelet Storage Pool Deficiency Gene Panel and Methodology Details 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: ABCC4, AP3B1, AP3D1, BLOC1S3, BLOC1S5, BLOC1S6, DTNBP1, FLI1, GFI1B, HPS1, HPS3, HPS4, HPS5, HPS6, LYST, NBEA, NBEAL2, ORAI1, PLAU, STIM1, STXBP2, VIPAS39, VPS33B, and WAS

Day(s) Performed