Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
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@email.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
Pulmonary hypertension (PH) is defined by increased mean pulmonary arterial pressure (greater than or equal to 25 mmHg at rest by right heart catheterization) that can be caused by various cardiopulmonary conditions or environmental exposures, such as hypoxia, pulmonary veno-occlusive disease, connective tissue disease, and exposure to appetite suppressants [PMID: 26318161]. Pulmonary arterial hypertension (PAH) is a specific type of PH characterized by the proliferation, obstruction and subsequent obliteration of small pulmonary arteries, resulting in progressive elevation of pulmonary artery pressure as the heart tries to counteract the resistance to blood flow. The blockage of blood flow eventually leads to progressive heart failure [PMID: 20301658, 27770446]. PAH is a rare condition, with an estimated prevalence of 15-60 affected individuals per million people [PMID: 26318161] and ~2.2 per million children [PMID: 27770446]. It can present with variable symptoms, including dyspnea, fatigue, syncope, chest pain, palpitations, leg edema and Raynaud phenomenon. Onset can occur at any age [PMID: 20301658]. PAH in children is a heterogeneous condition that can occur in association with cardiac, pulmonary or vascular disease or as part of a genetic condition, such as hereditary hemorrhagic telangiectasia [PMID: 27770446]. A clinical diagnosis of PAH is confirmed if pulmonary arterial hypertension is identified by right heart catheterization in the absence of other potential causes of PAH. PAH can be caused by genetic factors, environmental exposures, such as drugs, toxins, or infection, or from a combination of factors [PMID: 26318161, 27770446]. Heritable or genetic forms of PAH are incompletely penetrant and sex dependent, with symptoms more common in females [PMID: 20301658, 27770446], meaning that many individuals with a genetic form of PAH may not have a family history. Although pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) can have clinical findings that overlap with PAH, individuals with PVOD will eventually show symptoms of pulmonary capillary hypertension, such as orthopnea, crackles, pleural effusion, interstitial edema or septal lines [PMID: 20301658].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The diagnostic yield for comprehensive PAH next generation sequencing panels is not yet well-established, and depends on the panel's gene content and the patient's clinical features. The genes on this panel that are expected to have the highest yield of disease-causing variants in patients with PAH are BMPR2 and ACVRL1 [PMID: 27770446]. Copy number variants have been reported in some genes on the panel, including ACVRL1, BMPR2, ENG, SMAD4, and FOXF1, and deletions/duplications are believed to account for up to 50% of disease-causing BMPR2 variants associated with PAH [PMID: 16728714].
Utility
The clinical utility of the assay is to support a clinical diagnosis of pulmonary arterial hypertension and facilitate genetic counseling, including risk assessment for other family members.
Next generation sequencing: 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 Pulmonary Arterial Hypertension Panel includes sequence and copy number analyses of the following genes: ABCC8, ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, FOXF1 (including the upstream regulatory region of the FOXF1 gene), GDF2, KCNA5, KCNK3, RASA1, SMAD4, SMAD9, SOX17, and TBX4.
CPT Codes
81406x3, 81479
Collection
Collect
Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
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@email.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
Pulmonary hypertension (PH) is defined by increased mean pulmonary arterial pressure (greater than or equal to 25 mmHg at rest by right heart catheterization) that can be caused by various cardiopulmonary conditions or environmental exposures, such as hypoxia, pulmonary veno-occlusive disease, connective tissue disease, and exposure to appetite suppressants [PMID: 26318161]. Pulmonary arterial hypertension (PAH) is a specific type of PH characterized by the proliferation, obstruction and subsequent obliteration of small pulmonary arteries, resulting in progressive elevation of pulmonary artery pressure as the heart tries to counteract the resistance to blood flow. The blockage of blood flow eventually leads to progressive heart failure [PMID: 20301658, 27770446]. PAH is a rare condition, with an estimated prevalence of 15-60 affected individuals per million people [PMID: 26318161] and ~2.2 per million children [PMID: 27770446]. It can present with variable symptoms, including dyspnea, fatigue, syncope, chest pain, palpitations, leg edema and Raynaud phenomenon. Onset can occur at any age [PMID: 20301658]. PAH in children is a heterogeneous condition that can occur in association with cardiac, pulmonary or vascular disease or as part of a genetic condition, such as hereditary hemorrhagic telangiectasia [PMID: 27770446]. A clinical diagnosis of PAH is confirmed if pulmonary arterial hypertension is identified by right heart catheterization in the absence of other potential causes of PAH. PAH can be caused by genetic factors, environmental exposures, such as drugs, toxins, or infection, or from a combination of factors [PMID: 26318161, 27770446]. Heritable or genetic forms of PAH are incompletely penetrant and sex dependent, with symptoms more common in females [PMID: 20301658, 27770446], meaning that many individuals with a genetic form of PAH may not have a family history. Although pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) can have clinical findings that overlap with PAH, individuals with PVOD will eventually show symptoms of pulmonary capillary hypertension, such as orthopnea, crackles, pleural effusion, interstitial edema or septal lines [PMID: 20301658].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The diagnostic yield for comprehensive PAH next generation sequencing panels is not yet well-established, and depends on the panel's gene content and the patient's clinical features. The genes on this panel that are expected to have the highest yield of disease-causing variants in patients with PAH are BMPR2 and ACVRL1 [PMID: 27770446]. Copy number variants have been reported in some genes on the panel, including ACVRL1, BMPR2, ENG, SMAD4, and FOXF1, and deletions/duplications are believed to account for up to 50% of disease-causing BMPR2 variants associated with PAH [PMID: 16728714].
Utility
The clinical utility of the assay is to support a clinical diagnosis of pulmonary arterial hypertension and facilitate genetic counseling, including risk assessment for other family members.
Next generation sequencing: 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 Pulmonary Arterial Hypertension Panel includes sequence and copy number analyses of the following genes: ABCC8, ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, FOXF1 (including the upstream regulatory region of the FOXF1 gene), GDF2, KCNA5, KCNK3, RASA1, SMAD4, SMAD9, SOX17, and TBX4.
