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
Spontaneous pneumothorax can be an isolated non-syndromic finding or can be seen as a clinical feature in various syndromes including Loeys-Dietz syndrome (LDS) [Chambers 2015, PMID: 26493799; MacCarrick 2014, PMID: 24577266], Marfan syndrome [GeneReviews 2022, PMID: 20301510], vascular Ehlers-Danlos syndrome (EDS) [GeneReviews 2019, PMID: 20301667], and Birt-Hogg- Dubé syndrome (BHD) [GeneReviews 2020, PMID: 20301695]. The pulmonary features reported in individuals with these syndromes include pulmonary cysts, pulmonary blebs, and spontaneous pneumothorax. Intrafamilial variability has been reported. The associated features seen in each of these syndromes varies widely and pneumothorax may be the initial presenting complaint in some individuals.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The clinical sensitivity of comprehensive next generation sequencing panels is not yet well-established and is dependent on the panel's gene content and the patient's clinical features. The estimated detection rates are provided for pathogenic variants that can be identified by gene sequencing for probands meeting the clinical diagnostic criteria for specific disorders based on the gene content of this panel: ~92% for BHD (FLCN) [GeneReviews 2020, 20301695], >95% for vascular EDS (COL3A1) [GeneReviews 2019, PMID: 20301667], ~90% for LDS (sequence variant or copy number variant in TGFBR1 or TGFBR2) [GeneReviews 2018, PMID: 20301312], ~70-93% for Marfan syndrome (FBN1) [GeneReviews 2022, PMID: 20301510; Loeys 2010, PMID: 20591885]. Copy number variants are rarely identified in individuals with LDS and vascular EDS (both <1%), ~3-5% of BHD, and 2-9% of cases of Marfan syndrome have an exon-level or full gene deletion.
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
The heritable forms of spontaneous pneumothorax are most often inherited in an autosomal dominant manner. The CHOP Pneumothorax Panel focuses on genes that cause syndromic and non-syndromic spontaneous pneumothorax. It contains genes associated with various conditions that have been reported with pneumothorax as a clinical feature including Loeys-Dietz syndrome [PMIDs: 26493799, 24577266], Marfan syndrome [PMID: 20301510], vascular Ehlers-Danlos syndrome [PMID: 20301667], and Birt-Hogg- Dube syndrome [PMID: 20301695]. Additionally, familial spontaneous pneumothorax has been reported in individuals with pathogenic FLCN sequence variants in whom extra-pulmonary features of BHD are not detected [OMIM #173600]. This panel includes sequence and copy number analyses of the following genes and regions of interest: COL3A1, FBN1, FLCN, TGFBR1, TGFBR2
CPT Codes
81405x2, 81479, 81408
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
Spontaneous pneumothorax can be an isolated non-syndromic finding or can be seen as a clinical feature in various syndromes including Loeys-Dietz syndrome (LDS) [Chambers 2015, PMID: 26493799; MacCarrick 2014, PMID: 24577266], Marfan syndrome [GeneReviews 2022, PMID: 20301510], vascular Ehlers-Danlos syndrome (EDS) [GeneReviews 2019, PMID: 20301667], and Birt-Hogg- Dubé syndrome (BHD) [GeneReviews 2020, PMID: 20301695]. The pulmonary features reported in individuals with these syndromes include pulmonary cysts, pulmonary blebs, and spontaneous pneumothorax. Intrafamilial variability has been reported. The associated features seen in each of these syndromes varies widely and pneumothorax may be the initial presenting complaint in some individuals.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The clinical sensitivity of comprehensive next generation sequencing panels is not yet well-established and is dependent on the panel's gene content and the patient's clinical features. The estimated detection rates are provided for pathogenic variants that can be identified by gene sequencing for probands meeting the clinical diagnostic criteria for specific disorders based on the gene content of this panel: ~92% for BHD (FLCN) [GeneReviews 2020, 20301695], >95% for vascular EDS (COL3A1) [GeneReviews 2019, PMID: 20301667], ~90% for LDS (sequence variant or copy number variant in TGFBR1 or TGFBR2) [GeneReviews 2018, PMID: 20301312], ~70-93% for Marfan syndrome (FBN1) [GeneReviews 2022, PMID: 20301510; Loeys 2010, PMID: 20591885]. Copy number variants are rarely identified in individuals with LDS and vascular EDS (both <1%), ~3-5% of BHD, and 2-9% of cases of Marfan syndrome have an exon-level or full gene deletion.
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
The heritable forms of spontaneous pneumothorax are most often inherited in an autosomal dominant manner. The CHOP Pneumothorax Panel focuses on genes that cause syndromic and non-syndromic spontaneous pneumothorax. It contains genes associated with various conditions that have been reported with pneumothorax as a clinical feature including Loeys-Dietz syndrome [PMIDs: 26493799, 24577266], Marfan syndrome [PMID: 20301510], vascular Ehlers-Danlos syndrome [PMID: 20301667], and Birt-Hogg- Dube syndrome [PMID: 20301695]. Additionally, familial spontaneous pneumothorax has been reported in individuals with pathogenic FLCN sequence variants in whom extra-pulmonary features of BHD are not detected [OMIM #173600]. This panel includes sequence and copy number analyses of the following genes and regions of interest: COL3A1, FBN1, FLCN, TGFBR1, TGFBR2
