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 Congenital Diarrhea Panel tests for genetic alterations related to a group of rare enteropathies that manifest with chronic diarrhea early in life due to secretory, osmotic, or inflammatory causes. The majority of congenital diarrhea disorders (CDDs) are monogenic disorders inherited in an autosomal recessive manner and these conditions can be classified into four main types: defects in digestion and absorption, defects in enterocyte structure, defects in enteroendocrine cell differentiation, and defects in intestinal immune homeostasis [Canani 2015, PMID: 25782092].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The diagnostic yield 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.
Utility
The clinical utility of the assay is to support a clinical diagnosis of congenital diarrhea, 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 most common type of CDD is that in which there is a defect in digestion or absorption of nutrients and/or electrolytes which leads to chronic diarrhea [Canani 2015, PMID: 25782092]. Some of the conditions in this category targeted by the Congenital Diarrhea Panel include autosomal recessive glucose-galactose malabsorption (caused by pathogenic alterations in the SLC5A1 gene) and autosomal recessive congenital chloride diarrhea (caused by pathogenic alterations in SLC26A3). Defects in enterocyte structure are also targeted by the panel and include autosomal recessive congenital tufting enteropathy caused by mutations in the EPCAM gene [Canani 2015, PMID: 25782092]. The panel also tests for defects in enteroendocrine cell differentiation such as the enteric endocrinopathy due to proprotein convertase 1/3 deficiency caused by homozygous or compound heterozygous alterations in the PCSK1 gene. Defects in intestinal immune homeostasis are not included as part of the Congenital Diarrhea Panel. The Congenital Diarrhea Panel includes sequencd and copy numebr analyses of the following genes and regions of interest: APOB, ARX, CD55, CFTRφ, DGAT1, EPCAM, FLNA, GUCY2C, LCT, LIPA, MTTP, MYO5B, NEUROG3, PCSK1, PLVAP, PNLIP, RFX6, SAR1B, SBDS, SI, SKIV2L, SLC10A2, SLC26A3, SLC39A4, SLC51B, SLC5A1, SLC9A3, SPINT2, STX3, TTC37, UNC45A, and WNT2B.
φ Deep intronic variants c.3718-2477 and c.1680-886A>G and the intron 8 poly T tract in the CFTR gene are included in the analysis.
CPT Codes
81223, 81400, 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 Congenital Diarrhea Panel tests for genetic alterations related to a group of rare enteropathies that manifest with chronic diarrhea early in life due to secretory, osmotic, or inflammatory causes. The majority of congenital diarrhea disorders (CDDs) are monogenic disorders inherited in an autosomal recessive manner and these conditions can be classified into four main types: defects in digestion and absorption, defects in enterocyte structure, defects in enteroendocrine cell differentiation, and defects in intestinal immune homeostasis [Canani 2015, PMID: 25782092].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday to Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
The diagnostic yield 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.
Utility
The clinical utility of the assay is to support a clinical diagnosis of congenital diarrhea, 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 most common type of CDD is that in which there is a defect in digestion or absorption of nutrients and/or electrolytes which leads to chronic diarrhea [Canani 2015, PMID: 25782092]. Some of the conditions in this category targeted by the Congenital Diarrhea Panel include autosomal recessive glucose-galactose malabsorption (caused by pathogenic alterations in the SLC5A1 gene) and autosomal recessive congenital chloride diarrhea (caused by pathogenic alterations in SLC26A3). Defects in enterocyte structure are also targeted by the panel and include autosomal recessive congenital tufting enteropathy caused by mutations in the EPCAM gene [Canani 2015, PMID: 25782092]. The panel also tests for defects in enteroendocrine cell differentiation such as the enteric endocrinopathy due to proprotein convertase 1/3 deficiency caused by homozygous or compound heterozygous alterations in the PCSK1 gene. Defects in intestinal immune homeostasis are not included as part of the Congenital Diarrhea Panel. The Congenital Diarrhea Panel includes sequencd and copy numebr analyses of the following genes and regions of interest: APOB, ARX, CD55, CFTRφ, DGAT1, EPCAM, FLNA, GUCY2C, LCT, LIPA, MTTP, MYO5B, NEUROG3, PCSK1, PLVAP, PNLIP, RFX6, SAR1B, SBDS, SI, SKIV2L, SLC10A2, SLC26A3, SLC39A4, SLC51B, SLC5A1, SLC9A3, SPINT2, STX3, TTC37, UNC45A, and WNT2B.
φ Deep intronic variants c.3718-2477 and c.1680-886A>G and the intron 8 poly T tract in the CFTR gene are included in the analysis.
