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 Cholestasis Panel targets genetic causes of cholestasis including autosomal dominant Alagille syndrome [OMIM # 118450; OMIM # 610205] caused by pathogenic variants in the JAG1 or NOTCH2 genes. The panel also tests for autosomal recessive cholestasis caused by pathogenic variants in the ATP8B1, ABCB11, ABCB4, NR1H4, or TJP2 genes; bile acid synthesis defects caused by pathogenic variants in AKR1D1 or HSD3B; Dubin-Johnson syndrome [OMIM # 237500] (ABCC2), Cystic Fibrosis [OMIM # 219700] (CFTR), Icthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis [OMIM # 607626] (CLDN1), Niemann Pick [OMIM # 257220; OMIM # 607625](NPC1 and NPC2), Alpha-1-Antitrypsin deficiency [OMIM # 613400](SERPINA1), Familial hypercholanemia (OMIM # 607748] (BAAT), Lysosomal acid lipase deficiency [OMIM # 278000](LIPA), Citrullinemia type II [OMIM # 603471] (SLC25A13), and Arthrogryposis, renal dysfunction, and cholestasis 2 [OMIM # 613404; OMIM # 208085](VIPAS39 and VPS33B). In addition, this panel analyzes genes associated with a predisposition to diabetes and liver disease (HNF1A and HNF1B).
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The clinical sensitivity for sequence and copy number analysis targeting genes associated with cholestasis is not well-established and is dependent on the patient's clinical features and the panel's gene content.
Utility
The clinical utility of the assay is to support a clinical diagnosis of cholestasis, facilitate genetic counseling, and assess the risk to other first-degree relatives, as well as at-risk family members.
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 Cholestasis Panel includes sequence and copy number variant analysis of the following genes: ABCB4, ABCB11, ABCC2, AKR1D1, ATP8B1, BAAT, CFTRφ, CLDN1, HNF1A, HNF1B, HSD3B7, JAG1, KIF12, LIPA, MYO5B, NOTCH2, NPC1, NPC2, NR1H4, SERPINA1, SLC25A13, TJP2, UNC45A, VIPAS39, VPS33B.
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.
*Sequencing only. Deletion/duplication is not performed.
CPT Codes
81223, 81332, 81404, 81405x2, 81406, 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 Cholestasis Panel targets genetic causes of cholestasis including autosomal dominant Alagille syndrome [OMIM # 118450; OMIM # 610205] caused by pathogenic variants in the JAG1 or NOTCH2 genes. The panel also tests for autosomal recessive cholestasis caused by pathogenic variants in the ATP8B1, ABCB11, ABCB4, NR1H4, or TJP2 genes; bile acid synthesis defects caused by pathogenic variants in AKR1D1 or HSD3B; Dubin-Johnson syndrome [OMIM # 237500] (ABCC2), Cystic Fibrosis [OMIM # 219700] (CFTR), Icthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis [OMIM # 607626] (CLDN1), Niemann Pick [OMIM # 257220; OMIM # 607625](NPC1 and NPC2), Alpha-1-Antitrypsin deficiency [OMIM # 613400](SERPINA1), Familial hypercholanemia (OMIM # 607748] (BAAT), Lysosomal acid lipase deficiency [OMIM # 278000](LIPA), Citrullinemia type II [OMIM # 603471] (SLC25A13), and Arthrogryposis, renal dysfunction, and cholestasis 2 [OMIM # 613404; OMIM # 208085](VIPAS39 and VPS33B). In addition, this panel analyzes genes associated with a predisposition to diabetes and liver disease (HNF1A and HNF1B).
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The clinical sensitivity for sequence and copy number analysis targeting genes associated with cholestasis is not well-established and is dependent on the patient's clinical features and the panel's gene content.
Utility
The clinical utility of the assay is to support a clinical diagnosis of cholestasis, facilitate genetic counseling, and assess the risk to other first-degree relatives, as well as at-risk family members.
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 Cholestasis Panel includes sequence and copy number variant analysis of the following genes: ABCB4, ABCB11, ABCC2, AKR1D1, ATP8B1, BAAT, CFTRφ, CLDN1, HNF1A, HNF1B, HSD3B7, JAG1, KIF12, LIPA, MYO5B, NOTCH2, NPC1, NPC2, NR1H4, SERPINA1, SLC25A13, TJP2, UNC45A, VIPAS39, VPS33B.
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.
*Sequencing only. Deletion/duplication is not performed.
