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
Alagille syndrome (ALGS) [OMIM #118450; OMIM #610205] is an autosomal dominant condition involving the liver, heart, face, eyes, and skeleton. The major clinical manifestations of ALGS are cholestasis characterized by bile duct paucity on liver biopsy, congenital cardiac defects primarily involving the pulmonary arteries, butterfly vertebrae, posterior embryotoxon in the eye, and characteristic facial features include a prominent forehead, deep set eyes with mild hypertelorism, pointed chin, and saddle or straight nose with a bulbous tip. Other features that can be seen in patients with ALGS are renal, pancreatic, and central nervous system abnormalities [Spinner 2013, PMID: 20301450]. The clinical features seen in ALGS can be highly variable, even within the same family [Li 1997, PMID: 9207788].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
Next generation sequencing (NGS) of JAG1 and NOTCH2 detects a disease-causing variant in 89% and 1-2%, respectively, of individuals meeting the clinical diagnostic criteria for Alagille syndrome [Spinner 2013, PMID: 20301450]. Partial to whole gene copy number variants account for approximately 8-9% of molecular diagnoses of Alagille syndrome (7% in JAG1 and 1-2% in NOTCH2) [Spinner 2013, PMID: 20301450].
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, and assess the risk to other first degree relatives and to facilitate testing of 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 Alagille Syndrome panel includes sequence and copy number analyses of the following genes: JAG1 and NOTCH2. Pathogenic variants in the JAG1 gene are associated with the majority of cases of AGS. JAG1 is located on chromosome 20p12 and it encodes a highly conserved cell surface protein that is part of the Notch signaling pathway thought to regulate cell fate decisions in many cell types. The JAG1 protein acts as a ligand for the Notch transmembrane receptors. NOTCH2 is located on chromosome 1p12 and encodes a member of the Notch family of transmembrane receptors. These members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch 2 protein is a receptor for membrane-bound ligands thought to impact hepatic, vascular, and renal development.
CPT Codes
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
Alagille syndrome (ALGS) [OMIM #118450; OMIM #610205] is an autosomal dominant condition involving the liver, heart, face, eyes, and skeleton. The major clinical manifestations of ALGS are cholestasis characterized by bile duct paucity on liver biopsy, congenital cardiac defects primarily involving the pulmonary arteries, butterfly vertebrae, posterior embryotoxon in the eye, and characteristic facial features include a prominent forehead, deep set eyes with mild hypertelorism, pointed chin, and saddle or straight nose with a bulbous tip. Other features that can be seen in patients with ALGS are renal, pancreatic, and central nervous system abnormalities [Spinner 2013, PMID: 20301450]. The clinical features seen in ALGS can be highly variable, even within the same family [Li 1997, PMID: 9207788].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
Next generation sequencing (NGS) of JAG1 and NOTCH2 detects a disease-causing variant in 89% and 1-2%, respectively, of individuals meeting the clinical diagnostic criteria for Alagille syndrome [Spinner 2013, PMID: 20301450]. Partial to whole gene copy number variants account for approximately 8-9% of molecular diagnoses of Alagille syndrome (7% in JAG1 and 1-2% in NOTCH2) [Spinner 2013, PMID: 20301450].
Utility
The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, and assess the risk to other first degree relatives and to facilitate testing of 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 Alagille Syndrome panel includes sequence and copy number analyses of the following genes: JAG1 and NOTCH2. Pathogenic variants in the JAG1 gene are associated with the majority of cases of AGS. JAG1 is located on chromosome 20p12 and it encodes a highly conserved cell surface protein that is part of the Notch signaling pathway thought to regulate cell fate decisions in many cell types. The JAG1 protein acts as a ligand for the Notch transmembrane receptors. NOTCH2 is located on chromosome 1p12 and encodes a member of the Notch family of transmembrane receptors. These members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch 2 protein is a receptor for membrane-bound ligands thought to impact hepatic, vascular, and renal development.
