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 connective tissue disorders are a clinically and genetically heterogeneous group of conditions that manifest with symptoms in the skeletal, integumentary, ocular, respiratory, and cardiovascular systems. The Connective Tissue Disorder Panel focuses on genes that cause syndromic and non-syndromic connective tissue disorders. For both syndromic and non-syndromic presentations, there is a wide spectrum of severity and phenotypic expression of the connective tissue disorders.
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 panel's gene content and the patient's clinical features. 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% for vascular Ehlers-Danlos syndrome (EDS) [GeneReviews 2019, PMID: 20301667], ~50% for classic EDS [GeneReviews 2018, PMID: 20301422], ~70-93% for Marfan syndrome [GeneReviews 2022, PMID: 20301510; Loeys 2010, PMID: 20591885], ~96% for Loeys-Dietz syndrome [GeneReviews 2018, PMID: 20301312], and ~30% for familial thoracic aortic aneurysm [GeneReviews 2017, PMID: 20301299].
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
Connective tissue (CT) disorders can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. The CHOP Connective Tissue Sequence focuses on genes that cause syndromic and non-syndromic CT disorders. It contains genes associated with various conditions including Loeys-Dietz syndrome (LDS), lysyl hydroxylase 3 deficiency, Marfan syndrome (MFS), Myhre syndrome, Shprintzen-Goldberg syndrome (SGS), some forms of Ehlers-Danlos syndrome (EDS; vascular, classic, kyphoscoliotic, and arthrochalasia), familial thoracic aortic aneurysm (FTAT), and homocystinuria due to cystathionine beta-synthase (CBS) deficiency. The CHOP Connective Tissue Panel includes sequecne and copy number analyses of the following genes and regions of interest: ACTA2, B3GAT3, BGN, C1R, C1S, COL1A1, COL1A2, COL3A1, COL4A5, COL5A1, COL5A2, EFEMP2, ELN, EPHB4, FBLN5, FBN1, FBN2, FLNA, FOXE3, GATA5, LOX, MAT2A, MED12, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PLOD3, PRKG1*, SKI, SLC2A10, SMAD2, SMAD3, SMAD4, SMAD6, TGFB2, TGFB3, TGFBR1, TGFBR2.
*Copy number analysis is not performed for PRKG1.
CPT Codes
81405x3, 81406x2, 81408x5, 81407, 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 connective tissue disorders are a clinically and genetically heterogeneous group of conditions that manifest with symptoms in the skeletal, integumentary, ocular, respiratory, and cardiovascular systems. The Connective Tissue Disorder Panel focuses on genes that cause syndromic and non-syndromic connective tissue disorders. For both syndromic and non-syndromic presentations, there is a wide spectrum of severity and phenotypic expression of the connective tissue disorders.
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 panel's gene content and the patient's clinical features. 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% for vascular Ehlers-Danlos syndrome (EDS) [GeneReviews 2019, PMID: 20301667], ~50% for classic EDS [GeneReviews 2018, PMID: 20301422], ~70-93% for Marfan syndrome [GeneReviews 2022, PMID: 20301510; Loeys 2010, PMID: 20591885], ~96% for Loeys-Dietz syndrome [GeneReviews 2018, PMID: 20301312], and ~30% for familial thoracic aortic aneurysm [GeneReviews 2017, PMID: 20301299].
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
Connective tissue (CT) disorders can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. The CHOP Connective Tissue Sequence focuses on genes that cause syndromic and non-syndromic CT disorders. It contains genes associated with various conditions including Loeys-Dietz syndrome (LDS), lysyl hydroxylase 3 deficiency, Marfan syndrome (MFS), Myhre syndrome, Shprintzen-Goldberg syndrome (SGS), some forms of Ehlers-Danlos syndrome (EDS; vascular, classic, kyphoscoliotic, and arthrochalasia), familial thoracic aortic aneurysm (FTAT), and homocystinuria due to cystathionine beta-synthase (CBS) deficiency. The CHOP Connective Tissue Panel includes sequecne and copy number analyses of the following genes and regions of interest: ACTA2, B3GAT3, BGN, C1R, C1S, COL1A1, COL1A2, COL3A1, COL4A5, COL5A1, COL5A2, EFEMP2, ELN, EPHB4, FBLN5, FBN1, FBN2, FLNA, FOXE3, GATA5, LOX, MAT2A, MED12, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PLOD3, PRKG1*, SKI, SLC2A10, SMAD2, SMAD3, SMAD4, SMAD6, TGFB2, TGFB3, TGFBR1, TGFBR2.
