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@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 CHOP Comprehensive Pulmonary-Vascular Sequencing and Deletion/Duplication Panel is a next generation sequencing panel designed to identify underlying genetic variants associated with syndromic and nonsydromic causes of pulmonary disease. Pulmonary symptoms associated with conditions detectable through this panel include, but are not limited to, respiratory distress, chronic cough or wheeze, excessive mucus accumulation, chronic lung obstruction, chronic otosinopulmonary infection, bronchiectasis, surfactant deficiency, alveolar capillary dysplasia, alveolar proteinosis, and ciliary dyskinesia. Many of the conditions associated with pathogenic variants in genes on this panel have other clinical features which are characteristic of syndromic involvement.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The clinical sensitivity for comprehensive sequence and copy number analysis is not yet well-established and is dependent on the patient's clinical features and the panel's gene content. The estimated detection rates are provided for pathogenic variants that can be identified for probands meeting the clinical diagnostic criteria for specific disorders based on the gene content of this panel: 95-98% for Alagille syndrome [Spinner 2013, PMID: 20301450], >97% for cystic fibrosis [Ong 2017, PMID: 20301428], ~26-42% for dyskeratosis congenita [Savage 2016, PMID: 20301779], >95% for lysinuric protein intolerance [Font-Llitjos 2009, PMID: 18716612; Sperandeo 2008, PMID: 17764084], and 60-70% for primary ciliary dyskinesia [Zariwala 2015, PMID: 20301301].
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, to facilitate genetic counseling, to assess the risk to other first degree relatives, and to facilitate testing of at-risk family members. Molecular confirmation of a diagnosis may help guide recommendations for medical management and screening, and may help avoid unnecessary procedures.
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis is based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
Disorders associated with pulmonary-vascular disease can be inherited in an autosomal recessive, autosomal dominant, or X-linked manner. The CHOP Comprehensive Pulmonary-Vascular Panel contains genes associated with conditions including, but not limited to, respiratory distress syndrome, surfactant deficiency, alveolar capillary dysplasia, primary ciliary dyskinesia, interstitial lung disease, Alagille syndrome, cystic fibrosis, dyskeratosis congenita, and lysinuric protein intolerance. The panel includes sequence and copy number analysis of the following genes and regions of interest: ABCA3, ABCC8, ACVRL1, AP3B1, BMPR1B, BMPR2, CAV1, CCDC39, CCDC40, CCDC65, CCDC103, CCNO, CFAP298, CFAP300, CFTRφ, COPA, CSF2RA, CSF2RB, CTC1, DKC1, DNAAF1, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAAF6, DNAAF11, DNAH1, DNAH5, DNAH6, DNAH8, DNAH9, DNAH11, DNAI1, DNAI2, DNAJB13, DNAL1, DRC1, EIF2AK4, ENG, FARSB, FLNA, FOXF1$, GAS8, GDF2, HPS1, HPS4, INVS, ITGA3, JAG1, KCNA5, KCNK3, MARS1, MCIDAS, NKX2-1, NME8, NOTCH2, OAS1, ODAD1, ODAD2, ODAD3, ODAD4, OFD1, PARN, RASA1, RPGR, RSPH1, RSPH3, RSPH4A, RSPH9, RTEL1, SCNN1A, SCNN1B, SCNN1G, SFTPB, SFTPC, SLC7A7, SMAD4, SMAD9, SOX17, SPAG1, TBX4, TERC, TERT, TINF2, ZMYND10.
φ Deep intronic variants c.3718-2477 and c.1680-886A>G and the intron 8 poly T tract in CFTR are included in the analysis.
$ The upstream regulatory region of the FOXF1 gene is included in the analysis.
CPT Codes
81406 (x3), 81407, 81223, 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@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 CHOP Comprehensive Pulmonary-Vascular Sequencing and Deletion/Duplication Panel is a next generation sequencing panel designed to identify underlying genetic variants associated with syndromic and nonsydromic causes of pulmonary disease. Pulmonary symptoms associated with conditions detectable through this panel include, but are not limited to, respiratory distress, chronic cough or wheeze, excessive mucus accumulation, chronic lung obstruction, chronic otosinopulmonary infection, bronchiectasis, surfactant deficiency, alveolar capillary dysplasia, alveolar proteinosis, and ciliary dyskinesia. Many of the conditions associated with pathogenic variants in genes on this panel have other clinical features which are characteristic of syndromic involvement.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The clinical sensitivity for comprehensive sequence and copy number analysis is not yet well-established and is dependent on the patient's clinical features and the panel's gene content. The estimated detection rates are provided for pathogenic variants that can be identified for probands meeting the clinical diagnostic criteria for specific disorders based on the gene content of this panel: 95-98% for Alagille syndrome [Spinner 2013, PMID: 20301450], >97% for cystic fibrosis [Ong 2017, PMID: 20301428], ~26-42% for dyskeratosis congenita [Savage 2016, PMID: 20301779], >95% for lysinuric protein intolerance [Font-Llitjos 2009, PMID: 18716612; Sperandeo 2008, PMID: 17764084], and 60-70% for primary ciliary dyskinesia [Zariwala 2015, PMID: 20301301].
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, to facilitate genetic counseling, to assess the risk to other first degree relatives, and to facilitate testing of at-risk family members. Molecular confirmation of a diagnosis may help guide recommendations for medical management and screening, and may help avoid unnecessary procedures.
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis is based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
Disorders associated with pulmonary-vascular disease can be inherited in an autosomal recessive, autosomal dominant, or X-linked manner. The CHOP Comprehensive Pulmonary-Vascular Panel contains genes associated with conditions including, but not limited to, respiratory distress syndrome, surfactant deficiency, alveolar capillary dysplasia, primary ciliary dyskinesia, interstitial lung disease, Alagille syndrome, cystic fibrosis, dyskeratosis congenita, and lysinuric protein intolerance. The panel includes sequence and copy number analysis of the following genes and regions of interest: ABCA3, ABCC8, ACVRL1, AP3B1, BMPR1B, BMPR2, CAV1, CCDC39, CCDC40, CCDC65, CCDC103, CCNO, CFAP298, CFAP300, CFTRφ, COPA, CSF2RA, CSF2RB, CTC1, DKC1, DNAAF1, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAAF6, DNAAF11, DNAH1, DNAH5, DNAH6, DNAH8, DNAH9, DNAH11, DNAI1, DNAI2, DNAJB13, DNAL1, DRC1, EIF2AK4, ENG, FARSB, FLNA, FOXF1$, GAS8, GDF2, HPS1, HPS4, INVS, ITGA3, JAG1, KCNA5, KCNK3, MARS1, MCIDAS, NKX2-1, NME8, NOTCH2, OAS1, ODAD1, ODAD2, ODAD3, ODAD4, OFD1, PARN, RASA1, RPGR, RSPH1, RSPH3, RSPH4A, RSPH9, RTEL1, SCNN1A, SCNN1B, SCNN1G, SFTPB, SFTPC, SLC7A7, SMAD4, SMAD9, SOX17, SPAG1, TBX4, TERC, TERT, TINF2, ZMYND10.
φ Deep intronic variants c.3718-2477 and c.1680-886A>G and the intron 8 poly T tract in CFTR are included in the analysis.
$ The upstream regulatory region of the FOXF1 gene is included in the analysis.
