Skin biopsy or two T25 flasks of cultured fibroblasts from skin*
Blood – 2-3 mL in an EDTA (purple top) tube.
Bone Marrow - 2-3 mL in an EDTA (purple top) tube.
Saliva – please contact the lab regarding the availability of collection kits by emailing DGDGeneticCounselor@chop.edu.
DNA – 3 ug of DNA with a concentration of at least 50 ng/ul
*If the individual being tested has suspected or confirmed myelodysplasia or leukemia/lymphoma, or if the individual is the recipient of a donor (allogeneic) bone marrow transplant, cultured fibroblasts from skin are the preferred specimen to assess for constitutional genetic variants.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Clinical Features
The Inherited Thrombocytopenia Panel is a next generation sequencing (NGS) panel designed to identify underlying genetic variants associated with inherited thrombocytopenia. Inherited Thrombocytopenia is a heterogeneous condition that is characterized by low-platelet counts. Common symptoms include purpura, prolonged bleeding, hemoptysis and hematuria. Symptom presentation can occur at birth or in adulthood [Drachman 2004, PMID: 14504084].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday-Friday 9:00am - 4:00pm
Reported
28 days
Detection Rate
The diagnostic yield for comprehensive NGS panels is not yet well-established, and depends on the panel's gene content and the patient's clinical features. Estimated detection rates are provided for pathogenic variants in the genes on this panel that can be identified by gene sequencing for probands meeting the clinical diagnostic criteria for specific disorders:
Sitosterolemia: ~35% associated with ABCG5; ~65% associated with ABCG8 pathogenic variants [PMID: 22981120, 20521169]
Inherited thrombocytopenia: ~4.2% in ACTN1, % [PMID: 25361813]
Bernard-Soulier Syndrome + Platelet type von-Willebrand disease: Associated with GP1BA, GP1BB, GP9, detection rate unkown
Glanzmann thrombasthenia and bleeding disorder, platelet-type 16 (BDPLT16): Pathogenic variants in ITGA1, ITGA2B in 69-98% cases [PMID: 25827233]
Wiskott-Aldrich syndrome, X-linked thrombocytopenia: ~95% detection of pathogenic variants in the WAS gene
Utility
Identification of a causative pathogenic variant is a key component of the diagnostic evaluation for patients suspected of having an inherited thrombocytopenia.
Genomic DNA was extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing was performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis were based on the GRCh38 reference sequence. Sequencing data was processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
The Inherited Thrombocytopenia Panel includes analysis of the following genes: ABCG5, ABCG8, ACTN1*, ANKRD26* (including 5'UTR), AP3B1, CYCS, DIAPH1*, ETV6, FLI1, FLNA, GATA1, GFI1B, GP1BA, GP1BB, GP9, HOXA11, ITGA1, ITGA2B, ITGB3, MPL, MYH9*, NBEAL2, PRKACG, RBM8A, RUNX1, SRC*, SRP72, TPM4, TRPM7, TUBB1, WAS
* Sequence analysis only is performed for these genes.
CPT Codes
81339, 81404, 81406, 81479
Collection
Collect
Skin biopsy or two T25 flasks of cultured fibroblasts from skin*
Blood – 2-3 mL in an EDTA (purple top) tube.
Bone Marrow - 2-3 mL in an EDTA (purple top) tube.
Saliva – please contact the lab regarding the availability of collection kits by emailing DGDGeneticCounselor@chop.edu.
DNA – 3 ug of DNA with a concentration of at least 50 ng/ul
*If the individual being tested has suspected or confirmed myelodysplasia or leukemia/lymphoma, or if the individual is the recipient of a donor (allogeneic) bone marrow transplant, cultured fibroblasts from skin are the preferred specimen to assess for constitutional genetic variants.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Ordering
Clinical Features
The Inherited Thrombocytopenia Panel is a next generation sequencing (NGS) panel designed to identify underlying genetic variants associated with inherited thrombocytopenia. Inherited Thrombocytopenia is a heterogeneous condition that is characterized by low-platelet counts. Common symptoms include purpura, prolonged bleeding, hemoptysis and hematuria. Symptom presentation can occur at birth or in adulthood [Drachman 2004, PMID: 14504084].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday-Friday 9:00am - 4:00pm
Reported
28 days
Detection Rate
The diagnostic yield for comprehensive NGS panels is not yet well-established, and depends on the panel's gene content and the patient's clinical features. Estimated detection rates are provided for pathogenic variants in the genes on this panel that can be identified by gene sequencing for probands meeting the clinical diagnostic criteria for specific disorders:
Sitosterolemia: ~35% associated with ABCG5; ~65% associated with ABCG8 pathogenic variants [PMID: 22981120, 20521169]
Inherited thrombocytopenia: ~4.2% in ACTN1, % [PMID: 25361813]
Bernard-Soulier Syndrome + Platelet type von-Willebrand disease: Associated with GP1BA, GP1BB, GP9, detection rate unkown
Glanzmann thrombasthenia and bleeding disorder, platelet-type 16 (BDPLT16): Pathogenic variants in ITGA1, ITGA2B in 69-98% cases [PMID: 25827233]
Wiskott-Aldrich syndrome, X-linked thrombocytopenia: ~95% detection of pathogenic variants in the WAS gene
Utility
Identification of a causative pathogenic variant is a key component of the diagnostic evaluation for patients suspected of having an inherited thrombocytopenia.
Genomic DNA was extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing was performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis were based on the GRCh38 reference sequence. Sequencing data was processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
The Inherited Thrombocytopenia Panel includes analysis of the following genes: ABCG5, ABCG8, ACTN1*, ANKRD26* (including 5'UTR), AP3B1, CYCS, DIAPH1*, ETV6, FLI1, FLNA, GATA1, GFI1B, GP1BA, GP1BB, GP9, HOXA11, ITGA1, ITGA2B, ITGB3, MPL, MYH9*, NBEAL2, PRKACG, RBM8A, RUNX1, SRC*, SRP72, TPM4, TRPM7, TUBB1, WAS
* Sequence analysis only is performed for these genes.
